“Vaginal seeding” of infants born by caesarean section
BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i227 (Published 23 February 2016) Cite this as: BMJ 2016;352:i227
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It is bizarre that vaginal seeding should be discussed in this manner at all. Suddenly, seeding from the mothers vagina - which the baby would have got anyway had it been delivered the natural way, becomes a problem? Perhaps it comes about because of the unscientific assumption that every carried potential pathogens could kill us in one moment.
Are the authors unaware of the huge piles medical literature describing the crucial role of the vaginally seeded gut microbiome in the correct epigenetic step-wise programming of a new-born's immune development?
The biggest elephant in the room is the theatre itself and the people performing the caesarean. No matter the "sterile" procedures in place, the hospital environment has potential pathogens just as dangerous if not more so...., yet that is not part of the equation? Why is no thought given to the fact that the ignored flora of the theatre itself and the people "doing" the caesarean, might have potentially worse consequences to the baby? What would the result be if the same authors swabbed the theatres, gowns, gloves, the outside of mask and tested the air itself? Might that contain a very broad array of microbes that ideally we wouldn't want near any baby?
Doesn't it make sense that no matter what commensals a mother's vagina contains and even IF some expert considers them to be potentially dangerous, that the baby should FIRST be inoculated during a vaginal or after caesarean with what the mother has which she may well have immunity to , and provide further protection against, via colostrum? Might there be a good reason why vaginal seeding is the ideally designated method of primary microbiome seeding? And the lesser of two "evils"?
Surely, one of the reasons for the concern, is that the immune system of unseeded babies born by caesarean, are different, and many would say, are compromised and not ideal. Further, the literature we do have on the development of the neonatal immune system in both animals and humans shows very clearly that there are both short and long term problems which cannot be fixed when proper seeding does not take place.
The other point is that most caesareans, however they come about, are further complicated by giving the mother and babies routine IV antibiotics, which have the potential to totally undo seeding anyway, which is probably why seeding is only partially effective in changing the flora back towards vaginal "normal".
Solid foundations for immune development are crucial, and for humans a vaginal delivery is irreplaceable. In my opinion, the least the medical profession could do is get on board with what has served humanity wellin the past, instead of argue about purported lack of safety of trying to replicate that.
Competing interests: No competing interests
We read with interest the editorial by Cunnington et al (February 2016) on vaginal seeding after caesarean section. Although the contemporary evidence does not advocate introduction to medical practice, the logic in exposing the infant to the vaginal microbiota warranted debate. Indeed, similar logic prevailed with faecal enemas to treat Clostridium difficile infection. However, the concluding statement “the simplicity of vaginal seeding means that mothers can easily do it themselves” is questionable from a practical point. Following caesarean section, women often remain relatively immobile for several hours while the epidural wears off. Furthermore, those having undergone unplanned caesareans may be exhausted following prolonged or difficult labours. We, therefore, find it hard to believe that physically performing the seeding will be simple for all mothers. Perhaps this will emerge as a role for the father?
Competing interests: No competing interests
In the recent editorial by Cunnington et al. (“Vaginal seeding” of infants born by caesarean section. BMJ 2016;352:i227), the authors acknowledge the epidemiological associations between birth by Caesarean delivery and increased risk of obesity, asthma, and autoimmune diseases. These risks are also increased by alterations of the microbiota during early development. The authors also indicate that Caesarean-delivered newborns exhibit an unnatural microbiota composition, as demonstrated by us and others1,2, and state that “in theory, vaginal seeding might restore the microbiota of infants born by Caesarean section to a more “natural” state and decrease the risk of disease”, but that benefits of this practice now called “seeding” have not been proved. The authors warn against its widespread use without proper testing due to the risk of infections from exposure to vaginal commensals and pathogens, which the mother may carry asymptomatically.
Although we agree with Cunnington and colleagues in that risks are associated with the transfer of vaginal bacteria to the newborn, we would like to make the following clarifications:
1- As acknowledged in the editorial, the composition of the early microbiota of infants delivered by Caesarean is unnatural, resembling that of human skin instead of the vaginally acquired normal microbiota present in infants born naturally1,2.
2- We have demonstrated that the microbiota of Caesarean-delivered newborns is partially normalized during the first month of life if the newborn is exposed to maternal vaginal fluids3. As we indicate in our publication, the expected health restoration of the procedure has not been assessed yet, and we agree that this is a critical study to pursue.
3- Despite the infection risks that the authors correctly associate with our procedure, vaginal birth is the desired mode of delivery after a healthy pregnancy even in the case of GBS-positive mothers, which in the US are treated with antibiotics to deliver vaginally. Infection risks are acknowledged in our study3 and led us to the use of inclusion criteria (negative GBS test, no evidence of viral or bacterial infections, and acidic vaginal pH) stricter than the current standards for vaginal delivery.
4- We fully agree with the authors in that breast feeding should be encouraged and unnecessary antibiotics and Caesarean sections should be avoided.
More studies are needed to determine the health benefits of the multiple factors that shape microbial composition in infants, such as transfer of vaginal bacteria, breast feeding, and limited antibiotic usage. Interventions that alter natural processes such as vaginal birth should be practiced only when necessary, and the results of our study are a first step towards reducing the potential health costs associated with C-section.
Maria G. Dominguez-Bello, Ph.D.
Jose C. Clemente, Ph.D.
1. Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971-11975.
2. Backhed F, Roswall J, Peng Y, et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe. 2015;17(6):852.
3. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature Medicine. 2016.
Competing interests: New York University has filed an U.S. patent application (number 62161549) on behalf of Maria G. Dominguez-Bello, related to methods for restoring the microbiota of newborns. Jose C. Clemente declares no competing interests.
Thanks to the Authors for their response to our input on their article. I just wanted to clarify that when I said the February 2016 article in Nature provides in principle scientific support for vaginal seeding, I meant in terms of the primary aim of restoring microbiota which is what is thought to be lacking and not necessarily in terms of long term benefit. Of course, the infants from the study will need to be followed up to see if they derive the same benefit against allergies and autoimmune conditions similar to those who are exposed to microbiota naturally through vaginal birth.
My own opinion is like in the Editorial that the practice carries infection risks but we need to prove that the risks are indeed worse than vaginal birth before advising a blanket 'ban' and advising all staff not to do it. The warning issued through the BMJ Editorial is indeed welcome and will likely save a number of babies' lives but we need research evidence to give a balanced view on the issue. If we don't, the article in Nature could soon be posted on lots of lay websites and interpreted as in favour of the practice.
Competing interests: No competing interests
I am grateful to Clever Banda and Amali Lokugamage for their comments on the recent editorial "“Vaginal seeding” of infants born by caesarean section" (1). Both make reference a recent study published in Nature Medicine by Dominguez-Bello and colleagues which reports that vaginal seeding results in partial restoration of the microbiota of caesarian-born infants (2). I would like to assure them that we did not selectively ignore this evidence.
Our editorial article was written several months ago, was accepted for publication on 8th January 2016, and we approved the proofs on 19th January 2016. The article by Dominguez-Bello et al. was not published on-line until 1st February 2016. Banda suggests that we should consider this study as: "in principle providing scientific support for the practice of ‘vaginal seeding’." It certainly provides proof of concept that transfer of bacteria at birth can alter the developing microbiota. Indeed, it would be very surprising if this did not happen. However, it provides absolutely no evidence that this has any health benefit, as the authors themselves stress in the article. Furthermore, we cannot make any generalizations about safety of the procedure because only four caesarean-born infants received seeding, and they had all undergone screening for Group B streptococcus. Thus the findings of this study do not contradict any of the messages we aimed to convey in our editorial.
1. Cunnington A J, Sim K, Deierl A, Kroll JS, B Eimear, Darby J. “Vaginal seeding” of infants born by caesarean section BMJ 2016; 352 :i227
2. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A et al. Partial restoration of the microbiota of Caesarian-born infants via vaginal microbial transfer. Nat Med, 2016. doi: 10.1038/nm.4039.
Competing interests: No competing interests
The recent paper by Cunnington et al. [1] raises concerns about the risk of transmission of serious infections that is posed by the practice of ‘vaginal seeding’ for infants who are born by Caesarean section. This practice involves exposing these infants to vaginal fluids post-delivery and therefore to similar microbiota as infants born vaginally. Caesarian section delivery has been associated with various problems such as autoimmune and allergic diseases later in childhood which are thought to be related to this difference in microbiota exposure.[2] A recent study suggests microbiota can be partially restored in these infants by vaginal microbial transfer therefore in principle providing scientific support for the practice of ‘vaginal seeding’. [3]
Potentially serious infection in infants is a real risk and I think we should aim at providing safer alternatives to restore microbiota in infants born by Caesarian section.
Methods that have been proposed by some authors include administering probiotics to infants born by Caesarian section and encouraging breastfeeding. Breastmilk contains lactobacilli and bifidobacteria. Where breast milk is not feasible, probiotic containing milk formula can be used. [4] There is need for research into the appropriate strains of probiotics to ensure safety and efficacy.
Women who elect to use ‘vaginal seeding’ should be made aware of the risk of infection and should be assisted to make informed choices based on their medical history.
For example women who are known to carry or are at high risk of HIV, herpes simplex infection, chlamydia infection or have had a previous infant with Group B streptococcal septicaemia should be strongly discouraged from exposing their infants to vaginal fluids. Whether or not we should be advocating a blanket ‘ban’ on ‘vaginal seeding’ needs further scientific research as one might argue that the risks of infant exposure to harmful organisms in the majority of cases is similar to vaginal birth. [4]
References
1. Cunnington Aubrey J, Sim Kathleen, Deierl Aniko, Kroll J Simon, Brannigan Eimear, Darby Jonathan et al. “Vaginal seeding” of infants born by caesarean section BMJ 2016; 352 :i227
2. Neu J, Rushing J. Cesarean versus Vaginal Delivery: Long term infant outcomes and the Hygiene Hypothesis. Clinics in perinatology. 2011;38 (2):321-331. doi:10.1016/j.clp.2011.03.008.
3. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A et al. Partial restoration of the microbiota of Caesarian-born infants via vaginal microbial transfer. Nat Med, Feb 1 2016. doi: 10.1038/nm.4039. [Epub ahead of print]
4. Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG. The infant microbiome development: mom matters. Trends in molecular medicine. 2015;21(2):109-117. doi:10.1016/j.molmed.2014.12.002.
Competing interests: No competing interests
A sensible article and points I raise when teaching medical students. However I would like to point the authors to a recent article that they did not refer to which shows early evidence that the vaginal swab technique after caesarean section may partically restore/replete microbiota in infants. I believe mothers in this study were screened for potentially pathological vaginal flora to increase safety. (http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm.4039.pdf)
Competing interests: On the Advisory Board of Human Rights in Childbirth (NGO) and on the Board of Directors of the International MotherBaby Childbirth Organisation (UN recognised NGO). Both are charities.
Author's Reply to Butler
Butler makes several criticisms of our recent editorial article (1) on the role of health professionals in vaginal seeding.
Butler suggests that we ignored “huge piles [of] medical literature” which describe the necessity of the transfer of vaginal microbiota for the development of the newborn immune system. Unfortunately none of this literature is cited to support this statement. We acknowledge that the interaction between the microbiota and immune system is a fascinating and rapidly evolving field of research, and in our editorial we cited a review article on this topic (2). However, when we wrote our editorial we were unable to identify any published studies showing that the transfer of vaginal microbiota to newborn infants born by C-section produces any change in the development of the immune system. Shortly before our editorial was published, a small study was published in Nature Medicine, which showed that vaginal seeding can make the neonatal microbiota more similar to that of a vaginally born baby (3). This study did not examine any immunological parameters. Carefully controlled experiments in laboratory mice have been very important for demonstrating proof-of-principle that the microbiota can influence development of the immune system, but do not necessarily predict what will happen in humans exposed to much more complex external influences. It would be interesting if future clinical trials of vaginal seeding examine its influence on the development of the human immune system.
A second criticism seems to be that we neglected to consider the acquisition of nosocomial bacteria. This was certainly beyond the scope of the editorial. Again it would be a very interesting question for a clinical trial to examine whether vaginal seeding offers any protection from acquisition of nosocomial pathogens, and whether there is any trade-off with acquisition of antimicrobial resistant pathogens which may be carried by the mother.
Finally, we are criticized for not being “on board” with what has “served humanity well in the past” ie. natural vaginal birth. At no point in our article do we state or imply that C-section would be a generally preferred mode of delivery to vaginal delivery. In fact our concern about vaginal seeding is much more subtle than Butler implies. We are concerned that there may be a risk of neonatal infection following vaginal seeding, although the magnitude of this risk remains to be quantified. We believe that health professionals should not feel obliged to perform a procedure which may carry risk and does not have an established benefit. We acknowledge that parents may wish to perform the procedure themselves, and recommend that they should be allowed to do this if they understand the potential risk. Having cared for many infants with severe Group B Streptococcus and Herpes Simplex Virus infections, some of whom have died or been left with serious disabilities, we would not want any more infants to suffer the same fate because we had not warned about the potential for transfer of these pathogens by vaginal seeding. Unfortunately being born and giving birth are two of the most dangerous life events and infections account for a large proportion of neonatal deaths globally (4). Access to timely and better healthcare is one of the reasons why neonatal mortality is low in many well-resourced countries, and lack of access is one of the reasons why it is so dreadfully high in many resource-poor settings. Appropriate medical intervention in the process of childbirth undoubtedly saves lives, but we do need to ensure that interventions are genuinely appropriate. The only way to do this is by performing high quality clinical trials, and this is what is needed to establish the safety and effectiveness of vaginal seeding.
1. Cunnington A J, Sim K, Deierl A, Kroll JS, B Eimear, Darby J. “Vaginal seeding” of infants born by caesarean section BMJ 2016; 352 :i227
2. Maynard CL, Elson CO, Hatton RD, et al. Reciprocal interactions of the intestinal microbiota and immune system. Nature 2012; 489:231-41.
3. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A et al. Partial restoration of the microbiota of Caesarian-born infants via vaginal microbial transfer. Nat Med, 2016. doi: 10.1038/nm.4039.
4. Lawn JE, Blencowe H, Oza S, You D, Lee ACC, Waiswa P, et al. Every Newborn: progress, priorities, and potential beyond survival. Lancet 2014; 384: 189-205.
Competing interests: No competing interests