**1. Introduction**

Even though there is no global consensus on the optimal rate of cesarean section (CS), nevertheless the World Health Organization (WHO) advocates that this should be approximately 15% of all live births [1]. Many developed countries over the past 30 years are well in excess of this rate, without there being any significant improvement in either maternal or neonatal outcomes [2]. A study conducted on a worldwide scale using country-level data has found that as CS rates exceed 10% and increase up to 30% there is no essential effect on reducing maternal and neonatal morbidity or mortality rates. Moreover, the initial inverse relationship observed between CS rates and morbidity or mortality appears to be explained by socioeconomic factors [3].

The latest epidemiological data from Western countries has placed Greece among those with the highest CS rates reaching 54% for the year 2018 [4]. This rising CS trend however is not uncommon and represents a universal finding over the past decades [5]. The CS rate for 2019 in Canada was 29.1% [6] and for 2018 in the United States of America was 31.9% [7], whereas in the United Kingdom was 26.1% (**Figure 1**). Since an increasing number of women delay their first pregnancy

#### **Figure 1.**

*Cesarean section trends in selected OECD countries for the time period between 2000 and 2017. (Source: OECD Health Statistics 2019. Access: https://DOI.org/10.1787/888934017937).*

until after the third decade of their life and as the percentage of women with obesity is getting higher, this constitutes a high-risk environment for more CS births in the future [8]. At present, it is contemplated that one in three newborns are born with a CS worldwide.

### **2. Mode of birth and the neonate**

#### **2.1 Neonatal outcomes**

Cesarean birth has been associated with a variety of adverse neonatal outcomes in the literature. Fetal and neonatal complications include the increased risk for neonatal intensive care unit admission, respiratory morbidity, and mother-infant separation with all its consequences [9]. While CS delivery has been regarded as a method to reduce the risk of neonatal asphyxia, Kupari et al. [10] in their review found that the rate of neonatal intensive care admissions is higher after a cesarean birth. A recent study at a university based-tertiary hospital in Jordan showed that 50.5% of all deliveries were by CS, and from those 72% were performed at term. However, 30% of the newborns with a cesarean birth were admitted to the neonatal intensive care unit (NICU). The rate of NICU admissions was 23% among the elective ceserean births when compared to 43% among the emergency ceserean births. It is noteworthy that among the term neonates who were admitted to the NICU almost two thirds were born by elective CS between 37 and 386/7 weeks of gestation. Moreover, an estimated 18% of NICU admissions were complicated by sepsis and the mortality rate was 5% [11]. An earlier study also showed that an elective CS is associated with an almost two-fold increase in the rate of newborn transfers to the neonatal intensive care unit, and in the diagnosis of transient tachypnea of the newborn when compared with a planned vaginal birth [12].

Recent studies have highlighted the close interplay between host genetics, the prenatal environment and the route of birth on determining the newborn's microbiome at birth. There is emerging evidence that neonates born by CS have different hormonal, physical, bacterial, and medical exposures, and that these exposures can

#### *Cesarean Section and Breastfeeding Outcomes DOI: http://dx.doi.org/10.5772/intechopen.96658*

subtly alter their physiology. The short-term risks of CS include the altered immune system development, the increased likelihood of allergy, atopy and asthma, and the reduced diversity of the intestinal microbiome. It is not clear in the literature how these alterations might affect the children's health later on in life as young adults, although there is accumulating evidence of long-term effects. In the literature it is quoted that we have just started to realize the importance of the developing neonatal microbiome for the future health outcomes of the individual [13].

Formation of the microbiome begins *in utero* and the resulting disturbances may lead to changes in the fetal epigenetic programming [14]. Factors related to the labor and birth environment have been shown to influence the initial colonization process of the newborn microbiome. Studies have shown that there are distinct differences in the microbiome profiles of newborns born vaginally when compared to those born by CS [15]. The microbiome signature of pregnancy is dynamic and it changes throughout gestation even though the factors that regulate such changes are not yet fully understood [16]. It is possible that gestational changes in the microbiome may occur as a natural mechanism to prepare for the initial transfer of microbes to the newborns [15].

There is evidence showing that children born by a CS versus those born vaginally are more likely to develop immune-related disorders such as asthma and allergies [17], inflammatory bowel disease [17], and obesity [18]. These findings have led some researchers to suggest that the association between chronic disease and route of birth may be caused by alterations in the microbiome seeding of the neonate following the cesarean birth [19]. The hypothesis is that the mode of delivery affects the epigenetic state of the stem cells of the newborn, thus impacting on their plasticity and responsiveness later on in life [14]. It is important to note that neonates born to a CS when compared to neonates born vaginally have a smaller degree of similarity to the intestinal microbiome of their mother, which includes skin and oral cavity microbes, and bacteria from the operating room [18]. Furthermore, it has been shown that children with a slight exposure to their mother's vaginal microbiome during labor, even if they were delivered by a CS, have a reduced risk of developing asthma than those born with an elective CS [17].

There is evidence that the previously described differences in the microbiome remain long term, and the adults who were born with a CS have fecal microbiota that are distinctly different from those of adults who were born vaginally [20].

#### **2.2 Alterations to the neonatal microbiome**

It has been shown that for neonates born with a CS, their microbiome consists of different maternal microbiota than in neonates born vaginally. Bacteria from the operating room [18] have also been found to be present, while the antibiotics that women receive intrapartum to reduce the risk of post-operative infection may also affect the newborn's microbiome [21]. The question that has been raised in the literature is how the neonate can counter these alterations in its microbiome. An intervention that has been proposed involves the medical, midwifery and nursing personnel adopting a mother-friendly, family-centered approach in the operating room during the cesarean birth [15]. Early skin-to-skin contact with the neonate, early initiation of breastfeeding and support in a maternal-focused environment with a concurrent reduction of the time-spams of separation between the mother and the newborn while the neonate is hosted in the nursery, may also result in minimal disturbances to the neonatal microbiome. Breastfeeding after a cesarean birth may potentially be the way to minimize the adverse effects of the mode of delivery on the neonate's microbiome by promoting optimal early newborn microbiota formation. This may occur despite the effect of the antibiotics given to the mother

during the CS, which have been found to lower the counts of *Bifidobacterium* species in breast milk that are known to prevent infection and to provide anticarcinogenic capacities to the newborn [22].

Epigenetic programming during the perinatal period may induce very important physiological changes to the neonate. Potential adverse events may lead to epigenetic changes with serious implications for health and disease. There are studies as discussed earlier that suggest that epigenetic alterations are linked to early life environmental stressors such as the mode of delivery. However, it seems that epigenetic modifications due to perinatal environmental exposures can be potentially reversible [14]. It seems that during the first 3 years of life starting from conception to the second birthday of the child, there is a high turnover of the different types of colonizing bacteria, after which the microbiome is more stable [23].
