Vaginal Seeding After Cesarean Delivery

A promising method for increasing naturalization of neonatal microbiota

By Anne Kennard, DO, FACOG, ABOIM, Dipl-ABLM

REFERENCE

Song SJ, Wang J, Martino C, et al. Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding. Med (N Y). 2021;2(8):951-964.e5.

STUDY OBJECTIVE

To provide an adequately powered longitudinal study to determine the effect on neonatal microbiota of restoring exposure to maternal vaginal fluids after cesarean (CS) birth

KEY TAKEAWAY

Vaginal seeding of cesarean–born babies naturalizes their microbiota and can engraft multiple body sites.

DESIGN

Multicentered observational study

PARTICIPANTS

The study followed 177 babies from birth to 1 year (98 born vaginally, 79 born via cesarean delivery). Thirty of the cesarean babies were swabbed with a maternal vaginal gauze at time of birth. All seeded cesarean babies were negative for Group B Streptococcus and for sexually transmitted infections (STI) and had intact membranes at time of birth. Demographic details were as follows: • 101 babies were born in the United States, 20 in Spain, 50 in Chile, and 6 in Bolivia • 52% of babies were female, 48% male • 75% of vaginally born babies were breastfeeding dominant; 69% of cesarean-delivered babies and 53% of seeded-cesarean-delivered babies were breastfeeding dominant.

INTERVENTION

Vaginal seeding via vaginal maternal gauze of cesarean-born infants

STUDY PARAMETERS ASSESSED

Investigators obtained stool, mouth, and skin samples to analyze microbiota diversity at different body sites through use of compositional tensor factorization, which allows for analyzing diversity over time.

PRIMARY OUTCOME

Microbial trajectory in multiple body sites of seededcesarean babies compared to vaginally delivered babies vs cesarean births (not seeded) This study adds to the growing body of evidence that vaginal seeding partially restores infant microbiota of cesarean-born infants to approximate “ that of vaginally born infants.”

KEY FINDINGS

The trajectory of gut microbiota development in CS-born infants diverged from that of vaginally born infants through the entire 1st year of life. Seeded CS-born infants led to a developmental microbiota trajectory that more closely resembled that of vaginally born infants, most prominently in feces and skin. The effectiveness of seeding was variable depending on the bacterial taxa; for example, investigators identified that gut bacteria, including Bacteroides, Streptococcus, and Clostridium, were enriched in seeded CS infants, and these infants had microbes missing in CS-born babies. Other taxa did not prove to have an effective seeding and did not persist in the infant microbiome. The seeding differences were most prominent in the infant feces. During the taxonomic analysis, investigators observed a notable overlap between the species present in the maternal vagina and those present in sites including feces, skin, nose, and mouth of the baby, as compared with nonpregnant controls. This indicates that the perinatal vaginal microbiome is pluripotent and can engraft multiple body sites in the neonate. Of note, all 3 groups demonstrated maximum divergence of microbiota at time of birth and then converged over time to 1 year, with seeded CS babies more closely approximating, but not equaling, vaginally born babies.

TRANSPARENCY

Funding for this study was provided by C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, and Janssen.

PRACTICE IMPLICATIONS & LIMITATIONS

Over the past decade, research has demonstrated the multitude of ways that the microbiome can impact human health and the effects that mode of delivery can have on the microbiome. Differences in microbiome diversity and dysbiosis have been linked with childhood infections, cognitive and behavioral disorders, immune diseases, and potentially lifelong effects on obesity and metabolic disturbances.1-4 These differences may be due to many factors affecting the newborn’s microbiome, one of which is the mode of delivery.

Several studies have noted a difference in the microbiota and clinical disease burden in cesarean-born versus vaginally born children, although this idea is not without its detractors.5,6 Regardless, the practice of “vaginal seeding” has been developed, whereby gauze is soaked in maternal vaginal fluid and then wiped over the neonate’s eyes, mouth, and skin to inoculate the infant.

Up to this point, there has not been an adequately powered longitudinal study to demonstrate differences in the microbiota at different colonization sites. This study adds to the growing body of evidence that vaginal seeding partially restores infant microbiota of cesarean-born infants to approximate that of vaginally born infants.

While promising for potentially long-term health implications, the findings from this study may also influence future clinical practice recommendations. Presently, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (ACOG) both have formal statements that recommend against the practice of vaginal seeding. The American College of Obstetricians and Gynecologists Committee Opinion number 725 acknowledges that “the increase in the frequency of asthma, atopic disease, and immune disorders mirrors the increase in the rate of cesarean delivery, the theory of vaginal seeding is to allow for proper colonization of the fetal gut and, therefore, reduce the subsequent risk of asthma, atopic disease, and immune disorders.” However, it recommends against the practice outside of the context of an institutional review board–approved research protocol.7 The college does give guidance that if vaginal seeding is planned/performed, the patient should be tested and negative for diseases that can affect the newborn, including serum testing for herpes simplex virus and cultures for group B streptococci, Chlamydia trachomatis, and Neisseria gonorrhoeae. 7 The American Academy of Pediatrics (AAP) similarly states that “vaginal seeding is not recommended outside of a research study because of current lack of evidence of benefit and risk of infectious exposure” and should be strongly cautioned against in the setting of group B streptococci and herpes simplex virus, including education about the possibility of false negative testing for group B streptococci.8 The academy also notes that there is a significant influence of breastfeeding and maternal areola on the microbiome regardless of mode of delivery,9 and it questions the long-term consequences of cesarean delivery on human microbiota given that the available body of literature does not generally extend past age 2 years.8 The 2 position statements do not specifically address the body of literature that suggests mode of delivery has long-term effects on childhood and adult obesity and a related role between mode of delivery and microbiome.10-13

While vaginal seeding potentially could be a clinical tool to mitigate the rise of obesity, immune disorders, and neurodevelopmental disorders in the United States, it is unlikely that most obstetricians and pediatricians in the United

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States will be able to recommend and/or perform this practice with such oppositional position statements from professional organizations as cited above. In the current climate, recommending and/or performing vaginal seeding exposes the clinician to any potential liability that may occur and is unlikely to be recommended in a clinical setting outside of a research protocol.

The 2 position statements were published in 2017 and 2022, respectively, and may be updated in the future to reflect the translational research that this article and others have provided. However, for several more years, a tension may exist between clinicians’ awareness of the potential positive implications of this practice vs the potential liability. This tension may be mitigated in other settings, such as homebirth or a freestanding birth center with a certified nurse or licensed midwife, as well as ongoing pediatric care in a naturopathic setting as opposed to with a medical or osteopathic physician. An educated patient may also perform this practice independently, without the express knowledge or consent of the care team, though transparency is ideal so that health practitioners can properly test for infectious organisms and fully evaluate the infant if any concerns arise regarding potential neonatal infection.

One hopes that research protocols will continue to expand longitudinal data, including larger sample sizes and longer-term outcomes, with significant clinical differences and minimal harm noted. Accumulating ongoing clinical data will be key to changing the AAP and ACOG position statements so that

the practice of vaginal seeding may be used widely in clinical practice in the United States in a safe and effective way.

REFERENCES

1 Stokholm J, Blaser MJ, Thorsen J, et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat Commun. 2018;9:141. 2 Andersen V, Möller S, Jensen PB, Møller FT, Green A. Caesarean delivery and risk of chronic inflammatory diseases (inflammatory bowel disease, rheumatoid arthritis, coeliac disease, and diabetes mellitus): a population based registry study of 2,699,479 births in Denmark during 1973-2016. Clin Epidemiol. 2020;12:287-293. 3 Blustein J, Attina T, Liu M, et al. Association of caesarean delivery with child adiposity from age 6 weeks to 15 years. Int J Obes. 2013;37:900-906. 4 Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705-721. 5 Chu D, Ma J, Prince A, et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med. 2017;23:314-326. 6 Stinson LF, Payne MS, Keelan JA. A critical review of the bacterial baptism hypothesis and the impact of cesarean delivery on the infant microbiome. Front Med. 2018;5:135. 7 American College of Obstetricians and Gynecologists. Vaginal seeding.

Committee Opinion Number 725. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/11/vaginal-seeding. Accessed September 10, 2022. 8 Nolt D, O’Leary ST, Aucott SW. Risks of infectious diseases in newborns exposed to alternative perinatal practices. Pediatrics. 2022;149(2). 9 Pannaraj PS, Li F, Cerini C, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome.

JAMA Pediatrics. 2017;171(7):647. 10 Tun HM, Bridgman SL, Chari R, et al. Roles of birth mode and infant gut microbiota in intergenerational transmission of overweight and obesity from mother to offspring. JAMA Pediatr. 2018;172:368-377. 11 Masukume G, O’Neill SM, Baker PN, et al. The impact of caesarean section on the risk of childhood overweight and obesity: new evidence from a contemporary cohort study. Sci Rep. 2018;8:15113. 12 Kuhle S, Tong OS, Woolcott CG. Association between caesarean section and childhood obesity: a systematic review and meta-analysis. Obes Rev. 2015;16:295-303. 13 Mueller NT, Mao G, Bennet WL, et al. Does vaginal delivery mitigate or strengthen the intergenerational association of overweight and obesity? Findings from the

Boston Birth Cohort. Int J Obes (Lond). 2017;41:497-501.