Vaginal Microbiota and Lubricant Use During Labor

Abstract

The human microbiome profoundly influences health promotion and disease prevention. Improved DNA and RNA sequencing technologies have enhanced our knowledge on the composition of the various microbial communities that constitute the microbiome. The structure and stability of the vaginal microbiota is of particular importance during pregnancy and labor because maternal microbes form the basis of the neonate’s own microbiome during the birth process. Vaginal dysbiosis, or perterbations in vaginal microbial composition, that occurs during labor can lead to suboptimal neonatal colonization and may be linked to adverse health outcomes for infants and children, including asthma and obesity. Vaginal dysbiosis is linked with many factors, including the use of personal lubricants. Studies using cell and animal models show that lubricants can alter microbial composition as well as damage the integrity of vaginal epithelial cells. These findings are concerning because similar lubricants are frequently used during labor. However, the effect of lubricant use on vaginal microbiota in the health-care setting has not been studied. This article presents current evidence on vaginal microbiota during pregnancy with a focus on the influence of a common practice, lubricant use during labor. Areas for future research are presented, as well as practice and policy implications for perinatal health-care providers.

Introduction

The human body contains 10 times more microbial cells than human cells and 100 times more microbial genes than human genes (Lamont et al., 2011; Weinstock, 2012). Collectively, these microbes and their genomic material are called the human microbiome (Weinstock, 2012). The communities of microbes that comprise the microbiome profoundly influence health and certain essential biologic processes, including digestion and immunity, depend entirely on microbial involvement for success (Chung et al., 2012; Jumpertz et al., 2011). The symbiotic relationship between humans and microbes has been studied for centuries, but recent advances in technology have enhanced the ability to critically analyze the structure, stability, and function of each of the individual communities within the microbiome. Microbial DNA and RNA sequencing lie at the root of this emerging science. These molecular-based sequencing techniques surpass traditional culture-based methods in identifying and classifying microbes because they reveal the presence of taxa that may be difficult to cultivate or that may be present in diminutive numbers (Grice & Segre, 2012; Lamont et al., 2011). The relatively new methods have already illuminated a complexity in the microbial communities that was previously unrecognized.

Much research on the human microbiome has focused on the gastrointestinal (GI) and reproductive tracts, and findings are rapidly leading to more efficient, effective, and targeted care. For example, current recommendations on the use of probiotics for digestive health incorporate an increased knowledge of the structure of GI microbiota (Floch, 2014). Additionally, recent studies provide fundamental evidence on the composition of microbes in the vaginal environment during the reproductive years (Gajer et al., 2012; Ravel et al., 2010; Yamamoto, Zhou, Williams, Hochwalt, & Forney, 2009). These microbes, called the vaginal microbiota, have vital responsibilities for women’s health throughout the lifespan and are especially critical during pregnancy and birth because maternal microbes colonize the neonate during the birth process (Backhed et al., 2015; Dominguez-Bello et al., 2010). However, health-care providers may lack the foundational knowledge needed to appreciate the effect of vaginal microbiota on health, particularly during pregnancy. Without a basic understanding of the structure of vaginal microbiota, perinatal providers may not recognize that routine intrapartum practices can adversely modify the composition and function of the vaginal microbial environment. This article presents current knowledge about vaginal microbiota during pregnancy, its contribution to neonatal microbial colonization, and emerging evidence about the influence of intrapartum lubricant use on the vaginal microbiota.

Vaginal Microbiota in Pregnancy

Commensal microbes in the vagina serve at least two main functions during the reproductive years, infection prevention and neonatal colonization, and a unique composition supports this functionality (Lopes dos Santos Santiago et al., 2012; Witkin, Linhares, & Giraldo, 2007). From menarche to menopause, a diverse milieu of microbes inhabits the vaginal ecosystem but bacteria from the genus Lactobacillus typically dominate (Brotman et al., 2014; Gajer et al., 2012; Ravel et al., 2010; Yamamoto et al., 2009). Evidence shows that during pregnancy, the abundance of Lactobacilli remains dominant and may even increase, making vaginal microbiota less diverse overall (Aagaard et al., 2012; Hernández-Rodríguez et al., 2011; MacIntyre et al., 2015; Petricevic et al., 2012; Romero et al., 2014; Tamrakar et al., 2007). Lactic acid produced by Lactobacilli maintains a low vaginal pH of approximately 3.5 to 4. The acidic environment inhibits the proliferation of opportunistic pathogens that generally thrive at higher pH levels, thus achieving the critical function of preventing infection (O’Hanlon, Moench, & Cone, 2011; Witkin, et al., 2007).

Disruptions in the composition of vaginal microbiota, called vaginal dysbiosis, affect up to 50% of reproductive-aged women worldwide (Kenyon, Colebunders, & Crucitti, 2013). Dysbiosis typically entails decreased abundance of Lactobacillus spp. and elevated pH and can occur very rapidly (Gajer et al., 2012; Jespers et al., 2012; Lambert, John, Sobel, & Akins, 2013). Potential adverse effects from vaginal dysbiosis include discomfort, odor and itching, increased preterm birth, increased postpartum infection, poor outcomes in future pregnancies, and increased incidence of sexually transmitted infections, including HIV (Gallo et al., 2012; Institute of Medicine, 2007; Koumans et al., 2007; Leitich & Kiss, 2007). Factors associated with vaginal dysbiosis have been well documented (Figure 1) and include demographic factors, sexual activity, and hygiene practices (Baisley et al., 2009; Brotman, Ravel, Cone, & Zenilman, 2010; Brotman et al., 2014; Gallo et al., 2012; Koumans et al., 2007; Marrazzo, Thomas, Agnew, & Ringwood, 2010; Ravel et al., 2010). Knowledge about the factors that increase dysbiosis is critical during pregnancy for two reasons: (a) the link with increased preterm birth (Institute of Medicine, 2007) and (b) the vertical transmission of maternal microbes to the neonate (Backhed et al., 2015; Dominguez-Bello et al., 2010; Keski-Nisula et al., 2013).

Figure 1.

Factors associated with vaginal dysbiosis.

The initiation of microbial colonies in the neonate’s GI tract is partially due to physical contact with the maternal microbiome during the birth process (Backhed et al., 2015; Dominguez-Bello et al., 2010; Huurre et al., 2008). Despite this knowledge, very little research has been conducted on the composition of vaginal microbiota during labor. The few attempts to characterize vaginal microbes during labor used very small sample sizes (five or fewer women) and were cross-sectional in design, so changes over time were not investigated (Dominguez-Bello et al., 2010; Martín, Heilig, Zoetendal, Smidt, & Rodríguez, 2007). The paucity of longitudinal data reveals a gap in knowledge on the composition of the vaginal microbiota during labor and whether clinical interventions during labor influence the composition and stimulate vaginal dysbiosis. This gap in knowledge is critical because composition of vaginal microbiota during labor can influence neonatal health through neonatal GI tract colonization.

The Role of Maternal Microbiota in Neonatal Health

Although multiple sources influence the composition of GI microbiota over the lifetime (Figure 2), the birth process contributes the initial microbes that comprise the first neonatal microbial communities. During birth, neonates born vaginally gain initial exposure to microbes present in vaginal microbiota, including Lactobacillus spp. (Backhed et al., 2015; Dominguez-Bello et al., 2010; Huurre et al., 2008). Conversely, cesarean-delivered neonates acquire microbes associated with skin microbiota, typically transferred from parents and hospital staff (Backhed et al., 2015; Dominguez-Bello et al., 2010). Vaginal and skin microbial communities vary drastically in species composition and abundance, and these distinctions translate into differential short- and long-term colonization of the GI tract for vaginal versus cesarean-delivered neonates (Adlerberth et al., 2006; Azad et al., 2013; Backhed et al., 2015; Biasucci, Benenati, Morelli, Bessi, & Boehm, 2008; Dominguez-Bello et al., 2010; Fallani et al., 2010; Huurre et al., 2008; Jakobsson et al., 2013; Lif Holgerson, Harnevik, Hernell, Tanner, & Johansson, 2011; Penders et al., 2006).

Figure 2.

Influences on the development of gastrointestinal microbiota.

Intestinal bacteria that are generally recognized as beneficial to human health, including Bifidobacteria spp., are elevated in the GI tracts of neonates born vaginally (Backhed et al., 2015; Huurre et al., 2008; Penders et al., 2006). Additionally, over time, the GI microbiota of cesarean infants exhibit less overall diversity when compared with vaginally delivered infants (Adlerberth et al., 2006; Azad et al., 2013; Biasucci et al., 2008; Fallani et al., 2010; Huurre et al., 2008; Lif Holgerson et al., 2011; Penders et al., 2006). Implications of these differences in composition of GI microbiota are not well understood, particularly for infants and children, but knowledge is growing. For example, studies in adults reveal significant differences in the composition of GI microbiota between lean and obese people, people with and without GI disease, and people with and without metabolic disease (Lozupone, Stombaugh, Gordon, Jansson, & Knight, 2012; Moreno-Indias, Cardona, Tinahones, & Queipo-Ortuño, 2014). These differences may originate at birth based on initial exposure to microbes.

Emerging evidence shows that factors associated with the birth process, including altered neonatal gut colonization, may instigate physiologic changes that generate long-term health effects. For instance, children born via cesarean demonstrate increases in the likelihood of asthma, allergies, GI disease, obesity, and altered immunity when compared with children born vaginally (Blustein et al., 2013; Decker et al., 2010; Huh et al., 2012; Jakobsson et al., 2013; Renz-Polster et al., 2005; Salam et al., 2006; Salminen, Gibson, McCartney, & Isolauri, 2004; Thavagnanam, Fleming, Bromley, Shields, & Cardwell, 2008). Knowledge about the physiologic mechanisms responsible for these disparities remains elusive. However, early influences on the neonatal microbiome, particularly initial contact with skin microbiota as opposed to vaginal microbiota, likely impact the development of the neonate’s immune system and may be associated with these differences in health (Huurre et al., 2008; Neu & Rushing, 2011). Cesarean delivery represents the primary reason that neonates may experience suboptimal microbial exposure during birth; however, vaginal birth during a time of maternal dysbiosis may also affect neonatal colonization. For this reason, efforts to prevent dysbiosis during pregnancy and labor are important. However, studies have shown that women’s use of personal lubricant is associated with increased bacterial vaginosis (BV), the most common vaginal dysbiosis (Brotman et al., 2010; Marrazzo et al., 2010). This finding is of particular concern to perinatal providers because similar lubricants are frequently used in the hospital setting during labor.

Vaginal Dysbiosis and Lubricants

Intrapartum vaginal exams enable perinatal providers to assess the progress of labor. Providers apply lubricant to gloved fingers to decrease discomfort associated with the exams and during the exams, the lubricant coats the vagina and cervix. Vaginal exams are a very common intrapartum intervention despite a lack of evidence to support their use (Downe, Gyte, Dahlen, & Singata, 2013). The World Health Organization and the United Kingdom’s National Institute for Health and Care Excellence both recommend that vaginal exams be done no more than every 4 h during low-risk labor, but in practice, they are performed much more frequently (NICE, 2014; World Health Organization, 2015). In fact, evidence reveals that vaginal exams are often conducted every 2 to 3 h and almost 70% of laboring women receive more than the recommended number of exams (Borders, Lawton, & Martin, 2012; Shepherd & Cheyne, 2013). The findings related to the frequency of vaginal exams suggest an ongoing exposure to lubricants during labor, particularly in the hours immediately preceding birth. This repeated application of lubricant just prior to neonatal passage is problematic when considering the association between lubricants and changes to vaginal microbiota.

The underlying mechanism to explain the potential adverse relationship between lubricants and vaginal dysbiosis has not been studied experimentally in humans, but cell and animal models offer valuable information. For example, ingredients such as chlorhexidine, a microbicide added as a preservative to some commercial lubricants used in the health-care setting, can trigger dysbiosis. In lab tests, lubricants that contained chlorhexidine either significantly decreased or completely eradicated multiple species of beneficial Lactobacilli (Dezzutti et al., 2012; Fashemi, Delaney, Onderdonk, & Fichorova, 2013; Rabe & Hillier, 2000). The reported effects often occurred within 30 min of a single application of chlorhexidine. These findings demonstrate that although chlorhexidine may prolong the shelf life of lubricant products, the bactericidal effects on the vaginal microbial community as a whole must be evaluated. Two commonly used brands of lubricant, Surgilube and KY Jelly, contain chlorhexidine and can alter vaginal microbiota. However, even lubricants without chlorhexidine can disrupt the structure of vaginal microbiota because of the effects of lubricant properties, including osmolality, and other ingredients such as parabens.

Multiple in vitro studies that investigated the safety of over-the-counter vaginal lubricants found most products to be hyperosmotic, a property that can potentially damage the integrity of the epithelium (Adriaens & Remon, 2008; Begay et al., 2011; Cunha et al., 2014; Dezzutti et al., 2012; Fashemi et al., 2013). Apoptosis of epithelial cells can occur when intracellular fluid becomes depleted due to the high concentration of extracellular lubricant. The cytotoxicity results in epithelial sloughing and decreased protection from pathogens (Dezzutti et al., 2012). The conclusions based on cell models have been generally supported by animal studies as well.

Various components of lubricants, such as parabens, have been examined in animal models. These ingredients are typically promoted as benign and are added to give lubricants certain preferred properties, such as a decreased cold sensation upon evaporation (Moench, Mumper, Hoen, Sun, & Cone, 2010). Until recently, these ingredients were rarely considered to affect safety. However, a mouse model revealed certain inactive components of lubricants to be hyperosmotic and to increase susceptibility to vaginal infections (Moench et al., 2010). Studies using a macaque model demonstrated mixed effects of over-the-counter lubricants; one brand decreased Lactobacillus spp. abundance, but none of the products disrupted vaginal epithelia (Patton, Sweeney, & Hillier, 2014; Patton, Sweeney, Rabe, & Hillier, 1996). The findings from cell and animal studies suggest that lubricants can potentially disrupt vaginal microbiota in humans.

Results from human studies on lubricant use and dysbiosis are inconsistent but indicate a possible association. The few reported studies were observational in design, relied on personal recall, and varied on the timing of lubricant use. For example, one study queried participants on their lubricant use 1 day prior to specimen collection, while others reported on lubricant use at any time in the preceding month, or 3 months, or year (Brotman et al., 2010; Brown et al., 2013; Marrazzo et al., 2010; Mitchell, Manhart, Thomas, Agnew, & Marrazzo, 2011). Not surprisingly, the study that examined lubricant use closer to specimen collection showed a significant relationship between lubricant use and BV (Brotman et al., 2010; Marrazzo et al., 2010). Further human research on lubricant use during pregnancy is warranted and perinatal providers are perfectly positioned in obstetrical units to contribute knowledge and expertise to this research. The evidence generated from current and future research can impact obstetric practice.

Implications for Nursing Research, Practice, and Policy

Findings linking vaginal lubricants, dysbiosis, and epithelial damage have critical implications for pregnant women and must be considered by perinatal providers and researchers. Labor represents a profoundly sensitive time when the composition of vaginal microbiota can affect both maternal and neonatal health. Evidence shows that adverse changes in the composition of vaginal microbiota occur very rapidly but the return to baseline structure happens more slowly (Gajer et al., 2012). Therefore, repeated lubricant use during labor that elicits prolonged dysbiosis provides no opportunity for vaginal microbiota to return to a balanced and healthy composition prior to birth. Logically, extended periods of maternal vaginal dysbiosis during labor can translate into neonatal GI microbial patterns resembling those seen in neonates born via cesarean, potentially resulting in adverse health outcomes. These are essential considerations, but no studies have examined the effect of vaginal lubricant use in the health-care setting on maternal or neonatal microbiota. The liberal use of lubricants in obstetrics units necessitates the need for more research on these products.

A major difficulty in studying personal lubricants persists in their classification as medical devices. This classification allows manufacturers to omit the rigorous testing reserved for products that are classified as drugs (Cunha et al., 2014). Consequently, manufacturers are not required to list ingredients of the products. However, these challenges should not deter further research aimed at investigating the short- and long-term effects of lubricant use during labor. Initial studies should attempt to characterize vaginal microbiota at multiple times during labor, controlling for factors such as number of vaginal exams or dose of lubricant used. Alternatives to lubricants such as sterile saline can also be explored in subsequent intervention studies. Additionally, the link between maternal vaginal microbial composition and neonatal GI tract microbiota development should be investigated more thoroughly, and should include long-term outcomes such as asthma and obesity. Finally, epithelial damage from lubricant use leading to perineal trauma should also be investigated in observational studies. Findings from future studies can build evidence to support changes to clinical nursing practice.

If the deleterious effects of lubricants seen in cell and animal models translate into adverse outcomes for women and neonates, providers can implement safer practices and advocate for improved policies. Safer practices include limiting the number of vaginal exams or using alternatives to lubricants, such as sterile saline. Providers can also offer targeted patient education to promote individual actions that contribute to optimal colonization, such as breastfeeding, safe use of antibiotics, and supportive dietary habits.

Pilot work investigating the potential restoration of microbiota for infants born via cesarean has interesting implications. The small study found that infants swabbed with their mother’s vaginal secretions immediately after cesarean showed microbiomes in early life that more closely resembled those of vaginally born infants (Dominguez-Bello et al., 2016). However, more evidence needs to be available before any similar intervention becomes implemented in clinical practice. For example, the authors report that Lactobacillus iners was prevalent in the maternal vaginal fluid that was used to inoculate a few of the infants, yet consensus has not been reached on the influence of L. iners, its relationship to BV-associated bacteria, and whether it should be considered one of the more beneficial vaginal microbes. More research needs to be done to investigate the functions of the various species before determining the ones that will be most helpful for the development of the newborn microbiome.

At the institutional level, perinatal providers should advocate for evidence-based hospital policies that support more stringent guidelines on the frequency of vaginal exams for low-risk women and the use of lubricant in clinical settings. Finally, support for broader health policies that endorse the disclosure of ingredients in products used in the health-care setting is also necessary. Professional nursing organizations can provide resources to perinatal providers that are interested in shaping policy to improve patient safety (Abood, 2007). Armed with quality evidence on how lubricant affects vaginal microbiota, perinatal providers can improve obstetric care through safer practice, better education, and sensible policies.

Conclusion

Health outcomes throughout the lifespan are often influenced by factors related to pregnancy and birth. Therefore, we must carefully evaluate the most current evidence on the short-term benefits versus long-term risks of traditionally accepted intrapartum practices, such as frequent vaginal exams and liberal use of lubricants. Increased research during pregnancy and labor can expand our understanding of the intersection between the microbiome and human factors and the resulting influences on health promotion and disease prevention. This knowledge can then be leveraged into safer practices and targeted education that help to promote the implementation of effective policies that protect women and children.