Maternal Vaginal Flora Research Articles

Exposure to maternal vaginal flora during labor and long-term infectious morbidity of the offspring

Cesarean deliveries (CD) have been associated with an increased risk for offspring long-term infectious morbidity, as suboptimal exposure to maternal vaginal microbiome alters offspring immunologic milieu. We hypothesized that children who had varying exposure level to vaginal microbiome during labor, would differ in their long-term infectious morbidity.

Caesarian Vs Vaginal Delivery: From A Human Microbiota Perspective

The route of the birth delivery influences new born’s health. Children born via Cesarean section are at increased risk of developing asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies and leukemia. Part of these diseases is believed to be related to maturation of neonatal immune system. During vaginal delivery, the contact with the maternal vaginal and intestinal flora is an important source for the start of the infant's colonisation. During Caesarean delivery, this direct contact is absent, and non-maternally derived environmental bacteria plays an important role for infant’s gastro-intestinal colonisation. The primary function of microbial colonisation during the foetal period, intrapartum and after the birth is crucial in maturation and development of new-born immune system. This review supports the choice of the route of birth delivery and consequently favours a decrease in unnecessary Cesarean sections. It is crucial to provide this information to pregnant women and/or couples and health workers to make informed and educated decisions.

Targeted Development of Infant Microbiota on Formula Feeding: Modern Options

The review provides the analysis of recent publications covering the biological significance of infant microbiome and showing modern research technologies. Correlations of quantitative and qualitative characteristics of intestinal microbiota with delayed health issues were evaluated. Various concepts of newborn microbiome origin, timing, and stages of bacterial colonization of gastrointestinal tract were considered. Data on the role of delivery method on infant microbiota development is presented (including the significance of contamination with maternal vaginal flora where ontogenetic priority belongs to lactobacilli). It was revealed that Lactobacillus fermentum was the basis microflora providing the conditions for the subsequent successful colonization of the child’s intestines with obligate symbionts. The significance of breastfeeding in adequate microbiota development was confirmed. In case of mandatory formula feeding, it is necessary to enrich infant milk formulas with components that promote the selection of symbiotic microflora such as: long-chain polyunsaturated fatty acids, prebiotics, oligosaccharides, and probiotics of specific action. The innovative formula based on synbiotic/combiotic concept will be able to partially compensate impaired microbiota development in infant on mandatory formula feeding.

Increased risk of allergy hospitalization after cesarean delivery: A longitudinal study of 950,000 children

Cesarean delivery is increasingly implicated in the development of childhood allergies.1-3 In newborns, cesarean delivery prevents colonization by maternal vaginal and intestinal flora and is associated with mucosal dysbiosis.4 Mucosal dysbiosis is thought to impair immune tolerance and facilitate allergic sensitization.4,5 However, recent data suggesting that operative vaginal delivery is also associated with asthma and allergy challenge this hypothesis.2,6 Operative vaginal delivery does not cause mucosal dysbiosis given that fetuses born with forceps or vacuum instrumentation pass through the vagina and are colonized by maternal flora.

Association of Cesarean Delivery with Childhood Hospitalization for Infections Before 13 Years of Age

<h3>Objectives</h3> To determine the association between cesarean delivery and childhood infections up to 13 years of age. <h3>Study design</h3> We conducted a longitudinal cohort study of 731 803 children born between 2006 and 2016 at all hospitals in the province of Quebec, Canada. We followed children born by cesarean, operative vaginal, and nonoperative vaginal delivery up to 13 years of age. Outcomes included hospitalization for otitis media, respiratory, infectious enteritis, and other infections. We estimated hazard ratios with 95% CIs for the association between mode of delivery and childhood infections, adjusted for patient characteristics. <h3>Results</h3> At age 3-4 years, cesarean delivery was associated with a 1.07-fold greater risk of otitis media (95% CI, 1.03-1.11), a 1.15-fold greater risk of respiratory infection (95% CI, 1.09-1.22), and a 1.13-fold greater risk of infectious enteritis (95% CI, 1.03-1.25) compared with nonoperative vaginal delivery. However, operative vaginal delivery was associated with these same outcomes. Both cesarean and operative vaginal delivery were more strongly associated with infection hospitalization before age 1 year, but associations disappeared after 5 years. <h3>Conclusions</h3> Cesarean delivery is associated with infection hospitalization before but not after age 5 years. However, associations were also present for operative vaginal delivery, which suggests that mechanisms other than exposure to maternal vaginal flora explain the relationship.

The formation and the structure of the intestinal microflora

The bacterial population of the adult digestive tract consists mainly of two phyla: Bacteroidetes and Firmicutes. The formation of the intestinal microbiota covers a progressive evolution. In recent years, there is a widely held view that the bacterial colonization begins in utero. The presence of bacteria in the tissue of the placenta, in the foetal membranes, in the amniotic fluid and in the blood of the umbilical cord in healthy foetuses and newborns indicates the early exposure to the bacterial world as a first step of immune training. The colonization of the digestive tract continues and is amplified after birth. The vaginal birth induces an intestinal colonization that reflects the structure of maternal vaginal flora. The intestinal microbiota of C-section newborns is dominated by the maternal skin and oral flora but it also comprises the ecosystem of the skin of the medical personnel and the germs on the hospital surfaces. The breast milk contains live bacteria originating from the mammary canals, areola but especially from the maternal intestine, the latter being a natural source of colonization of the neonatal intestine. The physiological bacterial colonization of the intestine modulates gene expression of the epithelium for immune tolerance; it provides the host with nutrients and contributes to the maturing of the immune system.

Maternal vaginal flora during labor and its effect on gestational age and birthweight of neonates

Background: Identification of the abnormal colonization of the genital tract by a culture based approach has been recommended by the CDC 2000. This will definitely aid in the early recognition of mothers who need to be effectively treated which in turn will prevent newborn infections. Objectives were to study the pattern of maternal vaginal flora in labor and to study the outcome in the neonate.Methods: This study was conducted on 250 mothers in labor and their babies followed up till discharge in the departments of OBG and neonatology in a tertiary care medical college hospital, Deliveries by caesarean section were excluded.Results: Of the 250 babies, 70 were small for gestational age (SGA) and of these 60 (85.71%) were born to colonized mothers; whereas among the appropriate for gestation (AGA) babies, 110 (61.11%) were those born to non-colonised mothers. A statistically significant association was found between SGA babies and maternal colonization. Whereas relation between maternal colonization and gestational age did not show a statistically significant difference.Conclusions: This study shows us that maternal vaginal colonisation in labor significantly impacted the baby's weight with increase in small for gestational age babies being more among the colonised mothers. Hence, finding the organism in the maternal vaginal flora and treating it as per sensitivity might result in lesser incidence of SGA babies.

Pattern of maternal vaginal flora in labor and its effect on the newborn

Pattern of maternal vaginal flora in labor and its effect on the newborn

The influence of maternal vaginal flora on the intestinal colonization in newborns and 3-month-old infants

Aim: The role of maternal vaginal bacteria on the colonization of neonatal gut is still a matter of discussion. Our aim was to estimate the role of maternal vaginal flora on the development of intestinal flora in neonates and 3-month-old infants.Methods: Seventy-nine maternal–neonatal pairs were included in the study. Vaginal swabs were taken before the rupture of membranes after admission to the delivery ward. First neonatal stool (meconium) and stool at 3-month-old infants were collected and cultured. All samples were subjected to microbiological analysis for Streptococcus, Staphylococcus, Bifidobacterium, Clostridium (including C. difficile), Lactobacillus, Escherichia coli, Klebsiella pneumoniae, and Candida.Results: Maternal vagina was colonized mainly by streptococci (67%) followed by lactobacilli (58%) and Candida spp. (39%). Vaginal streptococci influenced the intestinal colonization in infants with staphylococci, C. difficile, and candida.Conclusion: Vaginal lactobacilli influenced colonization with C. difficile, and Candida. Vaginal flora is a potent factor influencing the development of bacterial flora in the neonatal and infantile gut. The extension of the observation period until 3 months of life allow to discover the potential changes in the intestinal flora of children.

944: Prelabored Cesarean section does not increase the prevalence of allergic disease in the offspring

Studies indicate prevalence of allergic disease is increased in children delivered by Cesarean section due to lack of exposure to maternal vaginal flora. Most of the studies either include elective cesarean section cases only or unclear if preoperatively labored cases were included in the Cesarean section group. Thus it is unknown as to increase of allergic disease in the offspring who had chance to be exposed to maternal vaginal flora prior to cesarean section. To compare the prevalence of allergic disease in the offspring delivered by Cesarean section but had labor prior to surgery with offspring delivered vaginal delivery. This study included 187 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire and delivery information was obtained via retrospective medical record review. Neonates have been followed for median 3.0 years postnatally (range 0.5-6.0). The levels of CB IgE were measured by the ImmunoCAP system. Results were adjusted sex, birthweight, gestational age at birth, season of birth, NICU care, parity, house-moving, breast feeding and maternal factors (age, atopy history, smoking/antibiotics during pregnancy). Of the 187 mother-neonate pairs from COCOA, 94 children (50.2%) were delivered by vaginal delivery. 29 children (15.5%) were delivered by Cesarean section following progression of labor. 28 (29.8%) of 94 was had allergic disease in offspring delivered vaginally and 9 (17.6%) of 29 had allergic disease in offspring was delivered by emergency Cesarean section. The major indication of emergency Cesarean section was labor dystocia. It means cervical dilatation was 8 cm. 22 (75.9%) of 29 had been ruptured membranes at the time of Cesarean section, and median labor duration until the emergency Cesarean section was 15.1 hour (range 0-22.3). The prevalence of allergic disease in the offspring who were delivered by Cesarean section but had prelabored was not significantly different when compared to vaginal delivery (p=0.449). Our finding suggests that labor prior to Cesarean section may provide the offspring with chance to be exposed to maternal vaginal flora.

The Vitamin D Antenatal Asthma Reduction Trial (VDAART): Rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children

There is intense interest in the role of vitamin D in the development of asthma and allergies. However, studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies. To address this uncertainty, the Vitamin D Antenatal Asthma Reduction Trial (VDAART) was developed. VDAART is a randomized, double-blind, placebo-controlled trial of vitamin D supplementation in pregnant women to determine whether prenatal supplementation can prevent the development of asthma and allergies in women's offspring. A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications, such as preeclampsia, preterm birth, and gestational diabetes. Women were randomized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3. Women who were between the gestational ages of 10 and 18weeks were randomized from three clinical centers across the United States — Boston Medical Center, Washington University in St. Louis, and Kaiser Permanente Southern California Region (San Diego, CA). Supplementation took place throughout pregnancy. Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events. Offspring are being evaluated quarterly through questionnaires and yearly during in-person visits until the 3rd birthday of the child. Ancillary studies will investigate neonatal T-regulatory cell function, maternal vaginal flora, and maternal and child intestinal flora.

Forceps birth delivery, allergic sensitisation and asthma: a population‐based cohort study

Studies indicate an increased risk of allergies among children born by caesarean section, possibly because immune development is altered by avoiding exposure to maternal vaginal flora. It is unknown if other obstetric interventions are associated with allergies. To assess associations between delivery with forceps assistance and development of atopy and asthma. In a population-based cohort of 1037 individuals born in 1972/73, atopy was assessed by skin-prick tests for common allergens at ages 13 and 32 years. A history of asthma was obtained at the same ages. Associations between birth with forceps assistance, atopy and asthma were assessed with adjustments for sex, head circumference at birth, parental atopy disease, birth order and socio-economic status. Children born using forceps were more likely to have atopy at ages 13 (53% vs. 44%) and 32 (68% vs 59%). They were also more likely to have asthma (21% vs. 11% and 23% vs. 16% at ages 13 and 32 respectively). Except for asthma at age 13, these associations were not statistically significant after adjustment for multiple confounding factors. Delivery with forceps assistance is associated with an increased risk of atopy and asthma, but the associations were weaker after adjustment for confounding factors. The previously reported association between caesarean birth and atopic disease may be due to confounding rather than altered exposure to maternal flora, although other factors associated with a difficult labour cannot be ruled out.

Probiotics in the Prevention of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a common gastrointestinal inflammatory necrosis affecting almost exclusively premature infants usually after oral nutrition has been started, for example, 10 day plus postpartum. Although the pathogenesis is incompletely understood, major risk factors include prematurity and incomplete bacterial colonization. Evidence has been shown that the premature infant because of rapid passage through the birth canal or because of delivery by cesarean section has an inadequate initial ingestion of maternal colonic and vaginal flora and therefore, an inadequate initial colonization with less diversity of bacteria phylla and fewer species of bacteria in the microbiota. As a result, they are more susceptible to environmental pathogens. In addition, prematures have immature intestinal defenses (glycocalyx, tight junctions, innate immune response, etc.) resulting in excessive inflammation in response to luminal stimuli. Recently, we reported that genes mediating the innate inflammatory immune response are developmentally expressed with an increase in toll-like receptors, signaling molecules and transgenic factors and decreased negative regulators of inflammation, which undoubtedly contribute to an excessive inflammatory response. Several clinical studies have suggested that the use of probiotics and ingestion of expressed maternal breast milk containing probiotics can help to stabilize colonization and to reduce the incidence and severity of NEC when given to premature infants at risk. Meta-analyses of multiple small studies strongly suggest a protective effect in the use of probiotics. A multicenter study in Taiwan suggests that Bifidobacteria infantis and Lactobacillus acidophilus in combination may prevent NEC. These meta-analyses suggest that these probiotics should be used in routine care of premature infants. Other clinicians, however, suggest caution, holding out for a single protocol multicenter trial before routine use can be suggested.

Asthma and Mode of Birth Delivery: A Study in 5-Year-Old Dutch Twins

Several studies report caesarean section (CS) to be a risk factor for childhood asthma. We used data from a large cohort of 5-year-old twins to examine the relationship between mode of birth delivery and asthma. The extent to which an infant is exposed to maternal vaginal flora may protect against the risk of developing asthma. Therefore, we expect a lower rate of asthma in twins born by vaginal delivery (VD) than those born by CS, and a lower rate of asthma in first-born twins compared to second-born twins by VD. Information on mode of delivery was obtained at the time of birth in a survey completed by the mother shortly after delivery. Information on history of asthma diagnosis by a physician was obtained by parental report when the twins were 5 years old. Complete data were available for 6330 first-born and 5438 second-born twins from birth cohorts 1991-2000. Full term first-born twins born by CS had a significantly higher risk of asthma compared to those born by VD, odds ratio=1.59 (95% CI=1.23-2.06). No significant differences were observed between CS and VD first-born twins when gestational age was less than 37 weeks, and no significant differences were observed between CS and VD second-born twins at any gestational age. No differences in asthma prevalence were found between first- and second-born twins both born by VD. CS may increase the risk of asthma to full term infants, however, the underlying mechanism is unclear.

Addressing the “new” NEC: Part I: Rediscovering the basics

Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens. These barrier defense capacities become destructive during disease processes like necrotizing enterocolitis (NEC) when an otherwise maturationally normal, yet dysregulated and immature, immune defense system is associated with high levels of certain inflammatory mediators like TNFa. In Part II, the authors will discuss the theoretical advantages of using rhG-CSF in managing NEC or sepsis by augmenting neonatal neutrophil number and killing capacity including an unexpected, paradoxical and potent anti-TNFa function that may serve to limit extension of tissue destruction without impairing bacterial killing capacity. The authors conclude by arguing that NEC may be the ideal disease process for testing whether a clearly defined clinical benefit of cytokine therapy can prove beneficial.

NEC: Part 2: Toward improving mucosal barrier defenses: rhG-CSF plus IgG antibody

Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens. These barrier defense capacities become destructive during disease processes like necrotizing enterocolitis (NEC) when an otherwise maturationally normal, yet dysregulated and immature, immune defense system is associated with high levels of certain inflammatory mediators like TNFa. In Part II the authors discuss the rationale for why rhG-CSF has theoretical advantages in managing NEC or sepsis by augmenting neonatal neutrophil number, neutrophil expression of Fcg and complement receptors, as well as phagocytic function and oxidative burst. rhG-CSF also has potent anti-TNFa functions that may serve to limit extension of tissue destruction while not impairing bacterial killing capacity. Healthy, non-infected neutropenic and septic neonates differ in their ability to respond to rhG-CSF; however, no neonatal clinical trials to date have identified a clear clinical benefit of rhG-CSF therapy. This manuscript will review the literature and evidence available for identifying the ideal subject for cytokine treatment using NEC as the model disease target.

Evidence of Probiotics in Prevention of Allergy and Asthma

Previous research into the causes of allergic diseases was mostly focussed on potential risk factors in the environment, with little success, however. Over the past 10 years, focus has therefore more been directed against protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. The composition of the microflora differs between healthy and allergic infants and in countries with a high and low prevalence of allergies. These differences are apparent within the first week of life, or even in the maternal vaginal flora during pregnancy and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Prospective intervention studies, in which the gut flora was modified from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.

The Intestinal Microflora During the First Weeks of Life

Bacterial colonization of the neonatal gastrointestinal tract begins during birth when the neonate comes into contact with the maternal cervical and vaginal flora. In infants delivered by Caesarean section, bacteria colonizing the neonate gastrointestinal tract are provided by the environment. The first bacteria encountered in the majority of healthy infants, are facultative anaerobes, which remain predominant during the first 2 weeks of life. Among them,Staphylococcus, EnterobacteriaceaeandStreptococcuswere the genera most commonly isolated from the newborn faecal flora at birth. Facultative anaerobic bacteria are followed closely byBifidobacterium sp. Clostridium perfringensis present within 2 days with an increase incidence in newborns delivered by a Caesarean section.Clostridium perfringensseems to be the precursor for installation of other anaerobic putrefactive bacteria, asBacteroidesand otherClostridium sp. The impact of Caesarean section and the period and quality of hospitalization are mainly implicated in changes of the normal newborn flora.Feeding seems to modulate the colonization pattern. In humans, breast milk plays a role in passive immunization of the neonatal intestine, and contains factors that promote the growth ofBifidobacterium bifidumin the intestinal flora. Formula feeding seems to promote implantation and persistance ofClostridium perfringens, and clearly enhances intestinal colonization ofC. difficilein newborns.

Genotyping may provide rapid identification of Escherichia coli K1 organisms that cause neonatal meningitis.

Escherichia coli K1 is the most common cause of gram-negative neonatal bacterial meningitis and septicemia. In an attempt to identify genetic markers in E. coli K1 that are associated with the capacity of the organism to cause neonatal meningitis, we used rRNA gene restriction patterns. E. coli strains isolated from the CSF of neonates with meningitis (n = 43) on two continents were compared to strains isolated from the blood of neonates with bacteremia who did not have meningitis (n = 29) and to isolates from the vaginas of asymptomatic pregnant women whose neonates remained without infection (n = 39). E. coli strains from CSF are genetically less heterogeneous than isolates from blood and the vagina: 44.2% of the CSF isolates belonged to only two types, whereas no more than two blood vaginal strains were of the same type. After HindIII digestion, a 14.9-kb rDNA-containing fragment was found in 81.3% of the strains from CSF vs. 28.0% of the isolates from blood and only 12.8% of the vaginal isolates (P = .001). Thus, genotyping might provide markers to identify organisms in the maternal vaginal flora that are highly likely to cause neonatal meningitis. This observation may have very practical implications for the early identification of these organisms in pregnant women and thus for the selective establishment of preventive measures per partum or for the early treatment of colonized neonates.

Ocular Traumas and Conjunctival Flora in Newborns, Comparing with the Maternal Vaginal Flora

The purpose of this study is to analyze the data concerning ocular injuries, congenital abnormalities, and the conjunctival flora of newborns. For this reason, randomised 224 newborns at Ankara Central Maternity Hospital were examined. We found 2,2 percent ocular congenital malformations and abnormalities 2,6 percent extraocular congenital malformation and abnormalities among these babies. The fewest lesions have been met in those delivered by the Cesarian section, and all delivered that were made by forceps and other equipment have had some lesions depending on the birth trauma. We also found a close correlation between maternal vaginal flora and newborn conjunctival flora.