The Effect of Birthing Method on the Infant Gut Microbiota

This student page has not been curated.

Abstract

Birthing methods, both vaginal and cesarean section play an essential role in the development of the infant. There has been recent interest and research surrounding the microbiome of the infant and how the bacteria they possess have a direct link to their delivery. The bacteria the infant ingests from the mother’s birth canal helps to build the immune system and better digest breast milk and solid foods. The changes of the vaginal microbiome during pregnancy give clues as to how similar the microbiome of that infant is and how important it be that the infant receives these bacteria.

The incidence of C-section relates to both the necessity of the procedure in times of emergencies, as well as elective surgery to potentially avoid the possible complications of birth. In the baby who is born via C-section, the microbiome that is developed is much less diverse than the baby born vaginally. These babies are at a higher risk of needing antibiotics, which can decrease bacterial diversity immensely. There is an increased risk for the development of asthma, allergies, obesity and other illnesses and diseases in those babies who are born C-section.

The Human Flora

The human body is made up of trillions of microorganisms (Knight, 2015). that affect both the functional and physiological aspects of the human, as well as their susceptibility to pathogens (Davis, 1996). Development of the human flora begins at childbirth and continues to develop well into adulthood. Bacteria thrive in certain environments, which results in large colonies among different parts of the body. The skin harbors a relatively consistent bacterial flora, with most bacteria remaining on the skin, while some attach to the nasal mucosa or deep hair follicles. In any given human being, there are about 10 trillion human cells to 100 trillion microbial cells and 20,000 human genes versus 20 million microbial genes (Knight, 2015).This equates to an average of three pounds of microbes in a human being with those microbes clearly outnumbering human cells. Having a vast number of microbes is imperative to the health of the human race, as they play a key role in fighting pathogens (Davis, 1996).

The formation of the human microbiota begins during the birthing process, making the vaginal microbiome a key role in that development. The vaginal microbiome is one that remains very subjective, as the bacteria present depends greatly on the woman’s age and race. (Akst, 2014). The most commonly found vaginal bacteria is the

Lactobacillus.

Lactobacilli act as the mediators in the vagina by interacting with the environment to sustain the traditional conditions necessary for the vagina (Nissl, 2014). These bacterium create lactic acid that helps to achieve the natural acidic pH. A disturbed pH prompts the Lactobacilli to produce more lactic acid to preserve the environmental conditions. Maintaining an acidic environment in the vagina helps to protect the woman from potentially pathogenic bacteria. While it has been thought that the Lactobacilli tend to be the most dominant bacteria in the vagina, race may determine how much is actually present. In a study among four hundred women, the majority were found to have a strain of Lactobacillus as the most dominant bacteria in the vagina (Akst, 2014). It was also discovered that Asian women and caucasian women were found to have a higher rate of the bacteria in their vaginal microbiome compared to Hispanic and black women (Akst, 2014). For those women whose vaginal bacteria was not dominated by Lactobacillus, other anaerobic bacteria were found that helped to maintain the acidic environment (Akst, 2011).

A second microbe that is found in vagina is Streptococcus agalactiae, which is a routinely healthy bacterium. A weakened immune system that results in fewer antibodies to fight the harmful pathogenic characteristics of this bacterium can produce damaging effects on the environment. These bacteria are hemolytic, which classifies them as potentially dangerous to neonates, who are highly susceptible to new microorganisms, who are born from a mother that is colonized (Stevens, 2002) (Kaplan, 2002).

Another microbe that is commonly found in the vagina is the Gardnerella vaginalis bacteria. While it can sometimes cause harmful effects, such as if it is passed to the newborn through birth, it is also found that in some cases, no harm may be done with a finding that about a quarter of all healthy women harbor this bacteria with no harm (Group B Strep Infection, 2012). This bacteria works to elevate the pH of the vagina and change the environment. They are known for creating protective biofilms against antibiotics and activate an inflammatory response that can displace Lactobacilli by raising the pH in the vagina (Saunders et al., 2007)

The Birthing History

The process of giving birth and how the birth happened dates back to hundreds of years ago where little was known about the safety and risks of different birthing methods. In the 1500’s century, cesarean section was a relatively new procedure. It was primitively used as an attempt to save a baby from a mother who was in the process of dying or was already dead, so it was not intended to save the mother’s life when it was first practiced (Sewell, 2013). Many of these C-sections took place on kitchen tables and beds, as access to hospitals was limited and even with access, the idea that the people working in the hospital and the hospital itself spread infection was enough to keep the surgery at home. There was a lot of trial and error as the C-section procedure evolved, including where to make the incision along the uterus and whether or not to leave stitches inside of the body. There were many post-operative infections that put the mother at risk, the most frequent of those being septicemia and peritonitis. As the use of C-section continued to be successful, they became the favored method of delivery instead of undergoing a prolonged or difficult labor. (Sewell, 2013). Today, the tendency to have an elected C-section is increasing, as it is believed that it will prevent complications that may occur with the mom or baby. (Leggitt, 2013).

In the United States, as of 2013, the number of vaginal births was 2,642, 892, whereas the amount of C-section births was 1,284,339, resulting in 32.7% C-section births (Births, 2015). Compared to the rate of C-sections in 2010, the rate has decreased slightly from the 32.8% it had been at (Martin, et al., 2012). In 2010, it was the first time since 1996 that the rate of C-sections had decreased. Between the years of 1996 and 2009, the rate of C-section increased by almost 60%. (Martin, et al., 2012). According to WHO, a safe rate of C-sections is between 10-15% (Gibbons, et al., 2010). Those countries whose rates are below are said to be underusing C-sections and those above, overusing. In the year 2010, only 14 countries fell within the 10-15% ideal range, whereas 54 countries were considered underutilizing and 69 countries were overusing (Gibbons, et al., 2010). It was concluded that low income and limited access to healthcare were the main reasons for underutilization.

The course of vaginal delivery has also changed with the access to new technology. Having the ability to monitor the fetus while in utero allows for birth to be more flexible with options such as water birth or home birth. In vaginal deliveries today, the use of vacuums and forceps are both still used, although the use has decreased. (Leggitt, 2013). Induction of labor is very common today, with about 40% of women being induced. Of that 40%, about 10% of the women have an actual need to be induced. (Leggitt, 2013) The overuse of a technique such as induction, shows the impatience that has developed overtime in regards to labor. Although it is sometimes necessary for health reasons, it is similar to the overuse of C-section; waiting to see how the body processes this natural experience may turn into a positive experience.

As the technology and the knowledge base surrounding birth continues to grow, we are constantly learning what may or may not be safe for both the baby and mom during and after childbirth. The history of childbirth and the different methods use contribute significantly to the research that continues today on what becomes important in childbirth. The idea that how a baby is born can greatly impact their life is a relatively new idea that is currently being researched. It may come across that a C-section can prevent potential problems with the baby or even with the mother, but it is becoming more clear that how the baby is born can actually predict what their health may encounter in the future.

Cesarean Section Birth

Figure 1. Cesarean delivery rates among different age groups
http://www.cdc.gov/nchs/data/databriefs/db35.htm#cesarean

Choosing how to deliver a child is a decision that has many factors. Delivering a child vaginally is generally the goal for childbirth, but other factors contribute. Implications for delivering via cesarean section include: labor that is not progressing, oxygen deprivation to the baby, breech or transverse position of the baby, multiple gestation, placenta problems and previous cesarean section delivery. Although having a C-section for these reasons may be necessary, many women choose to have a C-section to avoid delivery, have a planned delivery, or avoid possible complications of vaginal delivery (C-Section, n.d.).

In a newborn who is delivered via C-section, the microbes that are present vary. In a study where the cord blood of a healthy newborn delivered cesarean, the majority of the bacteria found were from the Enterococcus, Streptococcus, Staphylococcus, and Propionibacterium genera (Jiménez et al., 2005). Both Staphylococcus, and Propionibacterium are generally found in the skin flora. In a baby who is born C-section, their first exposure to bacteria are from the tools that are used for delivery and the skin of the people who touch them. Since they do not pass through the birth canal, they do not get to pick up the bacteria from her vaginal secretions and feces, building a very different microbiota than those babies born vaginally.

Innoculating Newborns with Mother's Vaginal Secretions

With continual research showing the benefits of a vaginal delivery, there has been new research developing in regards to inoculating a neonate born cesarean with the mother’s vaginal secretions. The goal of inoculation would be to provide those babies born via C-section the same bacteria that vaginal birthed babies receive to help build their microbiome. Dr. Maria Gloria Dominguez-Bello who is an associate professor in the Human Microbiome Program at the NYU School of Medicine has begun research on the inoculation process. Initial findings of inoculating newborns with gauze that has been saturated with the mother’s vaginal secretions found that their microbiomes did more closely resemble those who were born vaginally, but it was only a partial match (Goldberg, 2014). The number of bacteria observed from a C-section baby was doubled when they were exposed to their mother’s vaginal secretions, but those who were born vaginally still had six times the number of bacteria. In a vaginal birth, the baby is exposed to the mother’s bacteria for hours. This extended period of exposure gives the bacteria more time to incorporate itself into the neonate, allowing for this process to be maximized. In a cesarean delivery, it is important to note that it is likely that the mother, baby, or both has been exposed to antibiotics to prevent post op infection, possibly killing off any bacteria that had developed.

The NICU

The neonatal intensive care unit is a place for high-risk infants who are extremely vulnerable to infections. Infants who may need admission to the NICU include preterm, complications during delivery that require intervention on the newborn, underdevelopment, congenital anomalies, and any other issue that may compromise their health. Due to the extreme risk of infection because of their very immature immune systems, equipment, techniques, and procedures are done in a clean or sterile matter to essentially eliminate anything that could harm the baby.

In a study researching the neonatal intensive care unit, it was found that the microbial population within the unit closely resembled those found in the gut of premature infants. Many of the premature infants that are placed in the NICU have been delivered by cesarean section and many of the infants have been given multiple antibiotics to prevent infection. The NICU is to remain germ free, so frequent sterilization and disinfecting is performed to keep it this way. In a study performed by the University of California Berkeley (Eisen, 2014), fecal samples from two premature infants were sampled to analyze their microbial population. Samples from the most frequently touched surfaces in the NICU were also taken to compare to the fecal samples. The surfaces swabbed included the sink, feeding and breathing tubes, the hands of healthcare staff and parents, knobs on the incubators, and items from the nurse’s station, such as keyboards, mouses, and cell phones. The two fecal samples were compared to the surface samples and it was found that they were very similar. Among the surface samples, the bacteria collected from the feeding and breathing tubes were the most populated in the infant feces showing that these surface microbes relocated themselves into the newborn gut. Within both samples, it was also found that many of the bacteria harbored resistance genes that raise concern that they could be the same genes that produce antibiotic resistance. If the microbes found in the feces of the NICU patients are similar to those found on the surfaces, it raises a red flag for resistance, as those microbes have already resisted the disinfectants used to maintain sterility. Since all intensive care units are under strict protocol to maintain a sterile environment, it may be a matter of looking into the disinfectants used and changing them to see if that has an impact on reducing those bacteria that are already resistant.

Breastfeeding and Infant Formula

Figure 1. Bottle feeding baby
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048694.htm

Breastfeeding not only provides countless benefits for bonding between a mother and baby, but it also is provides key components for the neonate. Although breastfeeding is the ideal way to feed the newborn, it is not always possible. Some mothers find it uncomfortable or cannot produce enough milk and some health defects, such as cleft palate, can create difficulties when trying to breastfeeding. Formula is a desirable alternative to breastfeeding, as it provides adequate calories and many are fortified to include components such as iron. With this being said, breast milk is superior choice for feeding the newborn. The components of breast milk include proteins, carbohydrates, antibodies and other immune system components (Sonnenburg J, 2015) (Sonnenburg E, 2015). One of the most important components of breast milk is human milk oligosaccharides or HMOs. HMOs are the third most abundant component of breastmilk and have many functions when ingested (Vandenplas, 2002). In the body, HMOs act as receptors against pathogens, preventing attachment to the epithelium in the gut (Jantscher-Krenn, Bode, 2012). The infant cannot necessarily break down the HMOs mechanically, but the microbial population in the infant’s gut can digest these components and collect the energy from this (Sonnenburg J, 2015) (Sonnenburg E, 2015). This important component of breast milk has also shown to reach the colon in its original composition, providing benefits that support a healthy gut. (Jantscher-Krenn, Bode, 2012). It also serves to prepare the infant for solid foods by feeding the current microbiota and helping to create a population of Bacteroides (De Filippo, 2010). It has also been found that HMOs manage the shift of bacteria that takes place when solid food is introduced. Bacteroides can proficiently consume HMO’s and activate mucus-utilization genes, which absorb HMO’s (Marcobal, 2011 ) This allows the benefits of HMOs to be utilized by the newborn. When considering the benefits that this community of microbes has on the gut, it has also been discovered that consumption of breast milk has shown to contribute to a decrease the incidence of developing diarrhea, influenza, and respiratory infections during infancy, as well as type 1 diabetes, allergies, and multiple sclerosis. (Duke Medicine News and Communication, 2012).

A newborn’s gut flora is not only determined by their mode of delivery, but also through their feeding habits. The breast milk that a newborn ingests will aid in the development of colonies of essential microbes in the intestinal tract. These microbes facilitate in the absorption of nutrients, as well as immune system development. A study to determine how bacteria grows and develops in milk was performed at Duke comparing infant formula, cow’s milk, and breast milk. Each of the milk samples was incubated with two different strains of E. coli (Duke Medicine News and Communication, 2012). E. coli is a normal bacteria that lives in the human intestines and is beneficial in maintaining a healthy intestinal tract, as well as preventing harm from dangerous strains of E.coli (General Information, 2015). The results from the incubation showed that bacteria in all of the milk samples grew within minutes, but the colonization among each were different. In the breast milk sample, the bacteria created a biofilm(Duke Medicine News and Communication, 2012). Although some biofilms can be harmful, a biofilm within the gut can help to decrease infections and fight off disease (Hook, et al., 2012). In the cow’s milk sample and the infant formula sample, the bacteria grew individually, but there was no protective biofilm formed (Duke Medicine News and Communication, 2012). This study proved that breast milk is not only important for the nutrition and microbes in the gut, but also for those microbes that act as protectors against harmful pathogens.

In a fecal analysis of 98 Swedish infants that tracked them over the first year of life, there was a significant difference in the bacteria’s present in breastfed versus non-breastfed babies (Bäckhed, 2015). In those infants that were not breastfed, it was discovered that their gut bacteria predominantly consisted of Clostridia, further finding Roseburia, Clostridium, and Anaerostipes, which are frequently present in the adult gut microbiota. The breastfed infants were predominantly colonized with Bifidobacterium, which is commonly used in probiotics, and Lactobacillus, which flourishes when breast milk is ingested. By not breastfeeding and in turn developing a microbiota similar to an adult’s, it creates a very different set of microbes in those newborns who are breastfed and those who are not. It raises question as to whether or not breastfeeding allows for a longer evolution of the microbiota and that not breastfeeding shortens the evolution period (Bäckhed, 2015).

The choice to use infant formula occurs for many different reasons some being a necessity while others are preference. With the major difference between breast milk and infant formula being the lack of HMO’s in formula, there have been efforts to create a similar component to add into infant formula. Two components, galacto-oligosaccharides and inulin, have been added to some formulas in hopes to better mimic breast milk (Vandenplas, 2002). Although they do not provide all of the same benefits as breast milk, these added components have shown to promote the growth of Bifidi and Lactobacillus. The bacteria found in the newborn’s intestines are important for preventing infection and promoting healthy growth. Babies that are breast fed inherit this barrier of protection, while formula-fed infants have an ever changing gut microbiota that increases their risk of illness. Breastfed babies naturally have a healthy, beneficial gut microbiota. Those who are formula fed need help with decreasing the amount of illness-associated bacteria and increasing the amount of helpful bacteria. (New Infant Formula, 2012).

Probiotics and prebiotics have both been added to infant formulas with the effects being researched. Prebiotics are carbohydrates that maintain their structure through digestion and help to stimulate both growth and activity of the “good” bacteria in the gut. (New Infant Formula, 2012). Probiotics are actual live bacteria that also stimulate growth of the beneficial bacteria in the gastrointestinal tract. In a study comparing 172 healthy six-week old infants that were either breastfed, formula fed with prebiotics, or formula fed with probiotics, it was observed that a profound immunity was developed among the probiotic-fed infants, especially among those that were born cesarean. The probiotic formula contained Bifidobacterium animalis subspecies lactis, which is a favorable bacteria. In those infants, there was an increased amount of secretory, anti-rotavirus, and anti-poliovirus specific immunoglobulin A (IgA). Among the babies who were given the prebiotic formula, there was a mild improvement with an increased in some favorable bacteria and a decrease in disease-causing organisms. Incorporating probiotics into formulas have shown to have a positive effect on the newborn, which is very important for those babies who are not breastfed. It will be pertinent to continue researching which probiotics have the most outstanding effects in order to provide the most beneficial bacteria to the newborn.

Antibiotics and the Newborn

Antibiotics are used for a variety of reasons to defend the neonate from potentially harmful pathogenic bacteria. Since C-sections are an invasive procedure, prophylactic antibiotics are commonly used to help prevent infection in the mother, post op. Exposure of antibiotics to the mother also means exposure to the fetus and their bacterial community through the placenta, which puts the newborn at risk for a compromised microbiota. The gut microbes found in all humans play a critical role in cultivating a rapid production of granulocytes, which are white blood cells that focus on fighting infection (Deshmukh, et al., 2014). When a neonate is born with an already antibiotic exposed gut, the body adapts immediately by greatly increasing the amount of granulocytes in preparation of exposure to a vast number and variety of bacterium (Deshmukh, et al., 2014). In addition to exposure in utero, antibiotics are a common medication among babies and children with about one-quarter of all medications given to children falling under the category of antibiotics, one-third of those being unnecessary (Vangay, et al., 2013). This, again, puts the baby or child at risk for depletion of important and beneficial bacteria.

Whether the newborn is exposed to antibiotics directly during the postnatal period or indirectly prenatally, the microbiome changes accordingly. Essentially any kind of medication that enters the mother’s bloodstream will also enter the fetus’s bloodstream via the placenta, increasing the risk of exposure to antibiotics wide open. In a newborn receiving their first round of antibiotics, the diversity in the gut plummets (Sonnenburg J, E, 2015), putting them at high risk for infection. With a primary goal for antibiotic use to be prevention of further infection, these observations seem to contraindicate the use. When a repeat course of the antibiotics is given, the diversity that initially decreased tremendously does not decrease to the same effect as the first round due to adaptation by the microbiota (Sonnenburg J, E, 2015). Not only are these antibiotics killing the bacteria that are considered to be harmful, but they are also killing the beneficial bacteria. When given broad spectrum antibiotics, which is a general course of action when a source of infection is unknown, there is no cell specificity when deciding which bacteria should not be killed and which ones should.

Although the bacteria that are destroyed through antibiotics can recover, it is highly unlikely the microbiota will ever be the same (Sonnenburg J, E, 2015). In addition, the use of antibiotics in a newborn has been linked to increased risk for asthma, eczema, and obesity (Trasande, 2013) (Hoskin-Parr, 2013) . In a comparison done between children who received antibiotics as an infant and those who had no exposure to antibiotics there was a significant difference in their weights (Trasande, 2013). The children who had received antibiotics at six months or younger weighed much more than those who did not have any. Those who had received antibiotics after six months of age still weighed more than those who did not, although it was not as significant. In adults, fecal transplants have been utilized in treating severe bacterial infections (Deshmukh, et al., 2014). with a 92-95% success rate among a 200 case reports (The Fecal Transplant, 2015). Fecal transplants have not been performed in newborns, as it is difficult to determine whether a newborn that is critically ill is truly infected with bacteria (Deshmukh, et al., 2014). Until there is a more protective and successful method to treat a newborn without harming the microbiota, antibiotics will be administered whenever necessary (Deshmukh, et al., 2014).

References

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Edited by Meryl Jones, student of Rachel Larsen at the University of Southern Maine