Microbirthing: The " Vaginal Seeding" is growing fad, but thin evidence concerns physicians!

Every 4^th baby in UK is born by Caesarean Section. Parents of the Caesar babies are requesting a procedure called as ‘microbirthing’ or ‘vaginal seeding’.

Vaginal seeding involves taking a swab from mother’s vagina and swabbing it over babies face, eyes, mouth and skin immediately after caesarean birth.

This article is based on recent editorial in BMJ (BMJ 2016; 352:i227) by Cunnington A.J. et al “Vaginal seeding” of infants born by caesarean section. How should health professionals engage with this increasingly popular but unproved practice?

Our body is colonized with millions of microbes, collectively called as microbiota. They outnumber our cells by 10:1. The microbiota varies according to parts of our body and also person to person. As described by microbiology professor Graham Rook at University College London, we are designed to live in nature’s biodiverse ecosystem encountering our old microbial friends as part of our early immune education.

During the process of vaginal birth, specific species of good bacteria are transferred to the baby during and immediately after birth via the birth canal, immediate skin-to-skin contact and breastfeeding. This is the seeding of the baby's microbiome. The process heralds the training of baby’s immune system to recognize between ‘good’ and ‘bad’ bacteria and protect the neonate from diseases now and also in future.  Large epidemiological studies and reviews have concluded that babies delivered by C-section have moderately high risk of obesity, asthma, and autoimmune diseases, these  diseases being associated with alteration in microbiota.

For babies entering this world via a C-section, this microbial transfer from the mother to baby is interfered with or bypassed completely. According to the latest research if the baby is not seeded with mother’s bacteria, it can have significant health consequences. Dr Rodney R Dietert, Professor of Immunotoxicology at Cornell University says “Over the past 20-30 years, we've seen dramatic increases in childhood asthma, type 1 diabetes, coeliac disease, childhood obesity. We've also seen increases in Caesarean delivery. Does Caesarean cause these conditions? No. What Caesarean does is not allow the baby to be seeded with the microbes. The immune system doesn't mature, and the metabolism changes. It's the immune dysfunction and the changes in metabolism that we now know contribute to those diseases and conditions.”

So, many researchers advocate that even if vaginal birth is not possible, immediate skin to skin contact and breast feeding should be initiated.

A new documentary “MICROBIRTH” warns how our children are born could have serious repercussions for their lifelong health. “Microbirth” is a new sixty minute documentary looking at birth in a whole new way: through the lens of a microscope. Investigating the latest scientific research, the film reveals how we give birth could impact the lifelong health of our children. http://microbirth.com

In spite of all the hypotheses, we lack scientific proof at present. The newborn may be at risk of developing infection, being exposed to vaginal commensals that the mother maybe harboring without any symptoms. These include group B streptococcus (the most common cause of neonatal sepsis), herpes simplex virus, Chlamydia trachomatis, and Neisseria gonorrhoeae (the last two, causes of ophthalmia neonatorum). These pathogens may also be transferred on a vaginal swab, potentially voiding the protection offered by elective caesarean section.

Clinically we are aware of only one clinical trial going on, called as Potential Restoration of the Infant Microbiome (PRIME) trial. That study is expected to be completed in February, 2019.It is looking at the neonatal microbiota according to mode of birth, the women being screened beforehand for potential pathogens.

Dr. Cunnington, who is the lead author of the article, affirms the lack of sufficient evidence to put vaginal seeding into routine practice. Studies need to be sufficiently large, randomized and need follow up of many years before a recommendation can be made.  

In a statement Dr Cunnington says: "Demand for this process has increased among women attending hospitals in the UK - but this has outstripped professional awareness and guidance. At the moment we're a long way from having the evidence base to recommend this practice. There is simply no evidence to suggest it has benefits - and it may carry potential risks." He also believes in fully informing the risks and harm of this simple procedure to the patients who are demanding it.

He also emphasizes that there are other ways of   influencing baby’s microbiota at birth and “Encouraging breast feeding and avoiding unnecessary antibiotics may be much more important than worrying about transferring vaginal fluid on a swab.”

References:

http://www.criver.com/about-us/eureka/blog/april-2014/early-immune-education

http://articles.mercola.com/sites/articles/archive/2014/12/27/seeding-baby-microbiome.aspx

http://www.actionbioscience.org/genomics/the_human_microbiome.html

http://www.nytimes.com/2013/08/29/science/human-microbiome-may-be-seeded-before-birth.html?_r=0

http://www.huffingtonpost.co.uk/toni-harman/microbirth-babys-mircobiome_b_4947959.html

https://clinicaltrials.gov/show/NCT02407184?link_type=CLINTRIALGOV&access_num=NCT02407184

                                          

The dilemma of cervical ripening --Should it be oral or vaginal; should it be misoprostol or dinoprostone? A systemic review and network meta-analysis.

Induction of labor is considered  when the benefit of the procedure is surpasses the benefit of continuation of pregnancy. The rate of induction of singleton pregnancies in US in 2012 was 23.3%, almost more than double a decade ago. 

A primed and favorable cervix is a prerequisite for successful induction of labour.

Numerous methods are in use for cervical ripening to induce labour, that includes Foley’s catheter( Mechanical Method) to pharmacological methods including  the use of prostaglandins, oxytocin, and mifepristone.  Prostaglandin E₂, also known as dinoprostone, is the only prostaglandin that has been approved by the US Food and Drug Administration (FDA) for cervical ripening in labour induction.

Misoprostol, a prostaglandin E₁ analogue is often used as an off-label drug for inducing labour. Its use is fraught with many complications from uterine hyper stimulation, rupture and adverse FHR.

Many studies and reviews comparing the safety and efficacy of different methods have been conducted but the best agent and route is still unanswered.

The three most common agents widely in use are dinoprostone, Foley catheter and misoprostol (oral and vaginal). There are many RCTs comparing these different modalities but no large single trial has compared them all  head to head.

The study conducted by W Chen et al. is a systemic review and network meta-analysis of all the available RCTs comparing the five most commonly used methods,  published in the February issue of  BJOG: An International Journal of Obstetrics & Gynaecology .

The study aims at providing a comprehensive summary of the existing evidence to further inform clinical practice and aid in the design of future trials.

Network meta-analysis, in the context of a systematic review, is a meta-analysis in which multiple treatments (that is, three or more) are being compared using both direct comparisons of interventions within randomized controlled trials and indirect comparisons across trials based on a common comparator.

The selection criteria was including all the (RCTs) of cervical ripening during the induction of labour, evaluating rates of failure to achieve vaginal delivery within 24 hours, incidence of uterine hyperstimulation with fetal heart rate (FHR) changes, and rates of caesarean section. Studies including women with prelabour rupture of membranes were excluded.

Trials were excluded if they included the following cases: women with pregnancies less than  28 weeks of gestational age; non-cephalic presentations; multiple pregnancies; and women with previous caesarean sections, combination interventions, non-relevant outlook and conference papers, posters  and abstracts.

A total of 96 RCTs met the selection criteria resulting it a total of 17387 study subjects.

The interventions included in this review were Foley catheter, vaginal misoprostol, oral misoprostol, vaginal dinoprostone, and intracervical dinoprostone.

The primary outcome chosen for network metaanalysis were vaginal delivery not achieved in 24 hours; uterine hyperstimulation with FHR changes; and caesarean section.

The meta-analysis compared five different modalities of cervical ripening for induction of labour. It was seen that:

The rank probabilities of reducing the number of vaginal delivery not achieved in 24 hours according to different interventions from best to worst are vaginal misoprostol (100%), vaginal dinoprostone (95%), Foley catheter (59%), oral misoprostol and intracervical dinoprostone

The rank probabilities of not causing hyper stimulation with FHR changes from best to worst are Foleys catheter (90%), intracervical dinoprostone, oral misoprostol, vaginal dinoprostone, and vaginal misoprostol (99%).

The rank probabilities of different intervention in decreasing the rate of caesarean sections, from best to worst are oral misoprostol (83%), vaginal misoprostol (80%), vaginal dinoprostone, intracervical dinoprostone and Foley’s catheter.

Thus it was seen that although vaginal misoprostol was the most effective intervention for achieving vaginal delivery within 24 hours, but it came at the cost of highest rate of uterine hyperstimulation with FHR changes. Vaginal dinoprostone was second best vaginal delivery withi 24 hours.

Foley catheter was found to be the least likely to cause hyperstimulation, but is worse than both vaginal misoprostol and vaginal dinoprostone in achieving vaginal delivery within 24 hours.

Compared to Vaginal misoprostol, oral misoprostol had lesser incidences of uterine hyperstimulation but at the expense of slightly decreased number of vaginal deliveries in 24 hours, but this difference was not statistically significant.

In most countries misoprostol is not legalized to be used for induction of labor, because of the concerns of hyperstimulation. The study shows that oral misoprostol is safe in comparison to vaginal misoprostol and it also performed better than vaginal dinoprostone.The other advantage of misoprostol is it is effective, cheap, does not requires cold storage; the dose can be measured and precise as compared to vaginal route. It is the first drug of choice in developing countries.

Foley catheter has similar effect as oral misoprostol in achieving vaginal delivery.  It is inferior to prostaglandins in decreasing the C section rates but superior to use of Oxytocin alone. It may be highly indicated in women with high risk of Fetal hypoxaemia like postdate pregnancies, sickle-cell disease, pre-eclampsia, or intrauterine growth restriction, due to it’s least effect on hyperstimulation . It also has advantages in terms of cost and storage conditions, less stringent monitoring of uterine contraction and no medical intervention until it is expelled in labor.The drawback is high rate of chorioamnionitis, but metaanalysis was not performed due to lack of reporting of this data in most trials.  

Conclusion:

 

Vaginal misoprostol followed by vaginal dinoprostone are most effective methods for induction of labor beyond 28 weeks of gestation with intact membranes, in terms of achieving vaginal delivery. However they are also associated with  uterine hyper stimulation and adverse FHR requiring close monitoring.

Mechanical stimulation by Foley catheter was least effective method for vaginal delivery, along with oral misoprostol and intracervical dinoprostone, but caused the least uterine hyper stimulation and adverse FHR.

Oral misoprostol was the best method in terms of overall safety, least likelihood of uterine hyperstimulation and adverse FHR and reducing the likelihood of cesarean section than vaginal misoprostol. 

References:

 

Chen W, Xue J, Peprah MK, Wen SW, Walker M, Gao Y, Tang Y. A systematic review and network meta-analysis comparing the use of Foley catheters, misoprostol, and dinoprostone for cervical ripening in the induction of labour. BJOG 2016;123:346–354.

Hemming, K. and Price, M. (2016), Is it oral or vaginal; and should it be misoprostol or dinoprostone for cervical ripening? How to interpret a network meta-analysis. BJOG: An International Journal of Obstetrics & Gynaecology, 123: 355. doi: 10.1111/1471-0528.13533

http://www.improvingmedicalstatistics.com/meta_network.htm