C-sections, allergies, and probiotics

Student guest post by Shylo Wardyn

I recently read the book ‘Good Germs, Bad Germs’ by Jessica Snyder Sachs. I became intrigued by parts of her book that discussed how babies become colonized with bacteria during birth. The most interesting part was the differences between vaginally-delivered and Caesarean-delivered babies. It was not something I had ever thought of before. With my interest piqued, I did a Google scholar search to see what kind of research was being done on this topic. I stumbled upon an article looking at C-sections and risk of childhood allergies, namely asthma. I realized this would be the perfect topic for this assignment!

A little background information:

Asthma is a chronic inflammatory disorder of the airways that affects both children and adults. It is not known why some people develop asthma and others don’t. Rates of asthma have more than doubled from 1980 to 2004 in children <18, but since 2001 have held steady. It is noteworthy to mention that the definition of asthma was altered in 2001, as well (Moorman, et al., 2007).

A Caesarean section (C-section) is a surgical procedure in which an incision is made through the mother’s abdomen and uterus to deliver one or more babies. While C-sections are traditionally done when a vaginal delivery poses risk to the mother or baby, women can also elect to have a C-section instead of a normal delivery. C-section delivery rates account for 31.8% of all births in the United States; 2007 marked the 11th consecutive year of increase and a record high for the US (Hamilton B.E., 2009).

The neonatal period is critical for bacterial colonization of the intestines. Infants delivered vaginally acquire their intestinal flora from their mother’s vaginal and fecal flora, generally species of Bacteroides, Lactobaccilus and Bifidobacteria. This intestinal flora colonization is delayed in Caesarean delivered infants; consequently, their gut flora is abnormal for weeks to months. One study found that in Caesarean delivered infants at the age of 6 months, the colonization rate of Bacteroides was half that of infants in the vaginally delivered group (Grölund, 1999).

The research:

Gut normal flora has a significant impact on the immune system; normal flora strains have been shown to induce the production of IL-10, which has an important regulatory role in the development of the allergic immune response (Kalliomaki & Isolauri, 2003). This is the biological hypothesis behind the proposed association between C-sections and asthma. This issue has been studied, but results are conflicting. I found two meta-analyses that looked at the research to date. Thavagnanam (S. Thavagnanam, 2007) found a 20% increase in the risk of asthma in children who had been delivered by Caesarean. While Bager et al. also found a moderate increase in the risk of asthma after Caesarean, they did not attribute this to the increasing rates of C-sections (Bager, Wohlfahrt, & Westergaard, 2008). They felt that for this to be the case, C-section deliveries should be associated with all allergic outcomes, not just some of them. I felt that they discredited their study by stating this; they still found a biologically plausible and significant association between C-section delivery and asthma. A more recent Norwegian population-based cohort study confirmed a moderate association between C-section and asthma (Tollanes, Moster, Daltveit, & Irgens, 2008).

Probiotics and general remarks:

While there clearly needs to be more research about the exact role of gut flora in the development of allergies, an interesting area of research is in probiotics. Probiotics are cultures of beneficial bacteria of the normal gut flora. Studies have shown that probiotics administered to pregnant women and their newborns lead to lower rates of development of allergic diseases (including asthma). However, these studies looked at high-risk children; those that had a first degree relative or parent with any allergic disease (Kalliomaki, et al., 2001; Kuitunen, et al., 2009). I couldn’t find any randomized placebo-controlled trials with babies delivered by C-section as the group of interest. I think that would be a great study and would answer a lot of questions.

While it seems this is still a new area of research, I think the studies speak for themselves. If this information was more widely disseminated, maybe some women would think twice before electing to have a C-section. Maybe in the future, parents will be advised to give their newborns that were delivered by C-section probiotics. Or maybe everyone will be prescribed probiotics after taking broad-spectrum antibiotics….but that is for another blog!

Bager, P., Wohlfahrt, J., & Westergaard, T. (2008). Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy, 38(4), 634-642.

Grölund, M.-M. L., Olli-Pekka; Eerola, Erkki; Kero, Pentti. (1999). Fecal Microflora in Healthy Infants Born by Different Methods of Delivery: Permanent Changes in Intestinal Flora After Cesarean Delivery. Journal of Pediatric Gastroenterology & Nutrition, 28(1), 19-25.

Hamilton B.E., J. A. M., S.J. Ventura. (2009). Births: Preliminary Data for 2007.
Kalliomaki, M., & Isolauri, E. (2003). Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol, 3(1), 15-20.

Kalliomaki, M., Salminen, S., Arvilommi, H., Kero, P., Koskinen, P., & Isolauri, E. (2001). Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet, 357(9262), 1076-1079.

Kuitunen, M., Kukkonen, K., Juntunen-Backman, K., Korpela, R., Poussa, T., Tuure, T., et al. (2009). Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol, 123(2), 335-341.

Moorman, J. E., Rudd, R. A., Johnson, C. A., King, M., Minor, P., Bailey, C., et al. (2007). National surveillance for asthma–United States, 1980-2004. MMWR Surveill Summ, 56(8), 1-54.

S. Thavagnanam, J. F., A. Bromleyz, M. D. Shields and C. R. Cardwell. (2007). A meta-analysis of the association between Caesarean section and childhood asthma. Clinical and Experimental Allergy, 38, 629-633.

Tollanes, M. C., Moster, D., Daltveit, A. K., & Irgens, L. M. (2008). Cesarean section and risk of severe childhood asthma: a population-based cohort study. J Pediatr, 153(1), 112-116.

Comments

  1. #1 Stephen
    February 26, 2010

    Thank you Dr. Tara for building awareness with regard to C-Section / Gut Bacteria ( Second Brain ) / Allergies ( See below ).

    You may also find it interesting to look into the possibility that “We / Western Medicine ” are disconnecting the Embillical Cord to SOON after birth ..and it’s implications on Infant Health.

    While “Seeding” of the INFANT’s Immune System is important..and in my opinion the administration of probiotics should almost be SOP .. even for vaginally delivered Infants.

    May I just speak to a little known ( at least by Parents ) Term which describes a Lifetime sequence of multiple Diseases as a result of the Progression of a Progressive, Cumulative, Chronic Inflammatory Auto- Immune Disease > Called Allergy > Also called ALLERGY MARCH.

    Unfortunately, Allergy Parents of Allergy INFANTs are not made aware that…

    > Beginning at BIRTH > The Progression of Allergy Disease / MARCH = Allergy Parents = Allergy INFANT = Eczema > G.I. / colic > Ear > Respiratory > Rhinitis > Allergic ASTHMA ( Achoo & Ouch ).

    That while there is No Cure for Allergic ASTHMA…

    And that Asthma is principally the progression of Allergy MARCH which has gone UnTreated and allowed to migrate / exacerbate to Allergic Asthma….

    > That early ( Age 1-4 ) Food & Enviro Allergy Blood Testing / Treatment Intervension CAN actually Challange / Derail / PREVENT this Progression.

    Unfortunatley the Golden Window for Treatment is small i.e. 2-6 Yr before the Child receives a Life Sentence of Asthma.. followed by a Lifetime of Allergy / Asthma Misery.

    Still more unfortunate, because Cold, Flu & Allergy Symptoms are similar > when Allergy Parents take their Allergy Child to their Dr. > The “Usual suspects” of Cold & Flu are addressed / Symptoms Medicated > Leaving the progresion of Allergy MARCH InTact to Continue / Exacerbate UnAbated to possibly Allergic ASTHMA.

    To assit Allergy Parents of Allergy Children overcome this Diagnostic Barrier > My Company offers the ONLY F.D.A. Approved Allergy Blood Test ( AllergyMarchTopTen.com ) > which can be purchased ( $45.00 ) WithOut a Dr. Prescription.

    The AllergyMarchTopTen Test will FDA Test your Child for the Top Ten Allergens that signal the presence / emergence of Allergy March in your Child.

    Therebye alowing Allergy Parents to take their FDA / Positive Results to their Dr for expanded Allergy Blood Testing and ImmunoTherapy.

    Let us work together to Break the Legacy of Asthma in our Kids > via Early Testing ID & ImmunoTherapy.

    We already have the Means / Tools > Lets put them to Work !

    Best Health = Wealth Regards,

    Stephen

    Dec. 2008: Babies born by Caesarean section are more prone to asthma than babies delivered vaginally, suggests research published ahead of print in the Journal Thorax.

    The findings are based on almost 3,000 children, whose respiratory health was monitored until they reached the age of eight. By the time the children were eight years old, 362 (12.4%) had been diagnosed with asthma for which they had been prescribed inhaled steroids.

    Just 8.5% (247) children had been born by Caesarean section, but they were almost 80% more likely to have been diagnosed with asthma than their vaginally delivered peers.

    The association was even stronger for the 9% of children with two allergic parents and therefore a strong inherited predisposition to the disease.

    They were almost 3 X more likely to be Asthmatic by the time they were eight, compared with children whose parents were not allergic, who were around 36% more likely to have this diagnosis.

    Rates of asthma have soared in industrialized countries in parallel with a rise in Caesarean section births, which have increased from 5% in the 1970s to more than 30% in 2000.

    The authors say that the link between Caesarean section births and an increased risk of asthma may lie in the timing of the priming of the immune system: Caesarean delivery delays exposure to microbes.

    Previous studies investigating the link between asthma and Caesarean delivery have produced conflicting results.

    But the authors say that the number of children included in the study, the long monitoring period, and the definition of asthma to include inhaled steroids, strengthens their findings.

    “The increased rate of Caesarean section is partly due to maternal demand without medical reason,” say the authors.

    And they add: “In this situation the mother should be informed of the risk of asthma for her child, especially when the parents have a history of allergy or asthma.”

    Thorax

    Children born by caesarean delivery are at increased risk for developing asthma, particularly if their parents have allergies, according to a report published this month.
    C-section has been thought to be a risk factor for asthma, although the relationship is controversial, Dr. H. A. Smit, from the National Institute for Public Health and the Environment in Bilthoven, the Netherlands, and colleagues note in the report.
    Smit’s team analyzed data from 2917 children to assess the association between caesarean delivery and asthma or allergies at 8 years of age.
    Overall, 362, or 12.4 percent, of the children developed asthma at age 8, the researchers report, and 8.5 percent had been delivered by c-section.
    Overall, children delivered by c-section were 79 percent more likely to develop asthma than children born vaginally, the investigators found. The association between c-section and asthma was even stronger for children born to one or two allergic parents than for children born to parents without allergies.
    “Our results emphasize the importance of gene-environment interactions on the development of asthma in children,” Smit and colleagues conclude.
    “The increased rate of caesarean section is partly due to maternal demand without medical reason. In this situation, the mother should be informed of the risk of asthma for her child, especially when the parents have a history of allergy or asthma,” they wrote.
    SOURCE: Thorax, February 2009.

  2. #2 2nd Year Medical Student
    February 26, 2010

    These studies due seem to show a correlation. Though to give another plausible hypothesis apart from colonization of vaginal flora one physiological cause could be due to the immunosuppressive effects of the rise in steroids during parturition. We do know that term infants delivered via C-section are at increased risk of respiratory distress syndrome due to insufficient surfactant production. This is almost certainly from the insufficient cortisol i.e. lack of trauma to the mother as well as the much more abrupt transition from intrauterine to extrauterine life. Such steroids could plausibly lead to a slightly immunocompromised state for several days after delivery that induces healthy flora acquired from the environment.

    Some institutions are now routinely dosing the mother even if the pregnancy is at term with steroids before the C-section or giving it to the infant right after the procedure. It would be interesting to see if such a prophylactic measure designed for immediate respiratory function may ameliorate the correlation seen in these studies. I haven’t read the articles posted but i might also guess that C-section rates correlate well with formula access and use. And that the use of formula has been correlated with and other “over-active” immune systems. Did you know if the studies controlled for this possible confounder?

  3. #3 Luna_the_cat
    February 27, 2010

    @Stephen #1 –

    Possibly you really believe in your product. However, these forums are full of scientifically literate people who are aware that blood tests sold for “allergies” over the internet are notoriously unreliable, and usually designed to get people to buy programmes or products that they genuinely don’t need. Oh, and you don’t get to just make up syndromes (“Allergy MARCH”) and get taken seriously.

    Also, none of this has anything to do with the umbilical cord “being disconnected too soon” (and, what, you think that there are cultures which just sit around with the baby hanging off the cord after birth? Are you NUTS? Wait, don’t answer that).

    And finally: Random Capitalization Is *Not* Your Friend.

  4. #4 Jude
    February 28, 2010

    Two/thirds of my children have asthma; one’s asthma is severe. All three were delivered vaginally. This just seems silly to me.

  5. #5 Stephen
    March 1, 2010

    Luna > To your Comments

    Regardless of the fact that it is InterNet Offered ( it is the Digital Age after all )

    > The Allergy MarchTopTen.com Allergy Blood Test is the only F.D.A. Approved > At-Home Allergy Blood Test that can be purchased without a Dr. Prescription
    ( that is why it is so exciting ).

    This Kit’s F.D.A. Approval is REAL and confirms “Real Medicine” Vs the unreliable Tests you mention.

    In fact, the FDA actually “CALLed” DropYourAllergies.com to make sure that our InterNet Test Claims were correct / legal ..
    which they are .. and they left totally satisfied….
    If not surprised that they themselves were not aware of this Test’s FDA Status.

    Its results are the SAME i.e. F.D.A. Approved as any National Lab processing Allergy Testing.

    The thrust of my message speaks to the fact that Allergy Mothers who bring their Allergy Children into their Dr.’s ..

    only to find that their Dr.’s only address Flu & Cold Issues / Medicating Symptoms … leaving the progression of their Child’s Allergy March InTact to Continue / Exacerbate to possibly Allergic Asthma.

    Allergy Mothers of Allergy Children know that Allergy March is “ Real “ > Suggest look into.

    It is because of this Physician / Allergy Diagnostic impasse that we are telling Pro-Active Medical Consumers / Mothers > That YES they CAN take measures ( on their own) to Challenge the Progression of their Child’s Allergy MARCH to possibly Allergic Asthma.

    By bringing FDA Approved “Proof” that Allergy MARCH has begun in their Child > Physicians can “SEE” for themselves and are then move confidently forward with further expanded Allergy Blood Testing and Immuno-Allergy DROP neutralization.

    Case in Point > Regarding Jude’s 3 ASTHMA Children ( See below )…

    I would guess that Allergy Mother / Jude experienced this same situation as I have outlined…

    That the progression of her Child’s Allergy MARCH ( which begins at Birth ) was allowed to migrate / exacerbate to Allergic Asthma ( usually before Age 5-7 ) without be challenged with early Allergy Blood Testing and Immuno-Allergy Drops.

    Never forget > Today’s Progression of Allergy MARCH = Tomorrow’s Allergic Asthma.

    Regarding my Umbilical Cord comment
    > It is not Allergy Related > But speaks to yet another “Interesting Fact “ much like Dr. Tara’s new awareness relating to the C-Section / Asthma Link.

    Further to Jude’s 3 Asthma Children …

    > The above C-Section / Asthma Research Comments do not correlate 1 to 1 / directly to C-Section to Asthma… but only mention the “ increased Incidence” of Asthma when C-Sections occur .

    The fact that her 3 Children have Asthma is prob a reflection of a Strong Genetically PreDisposed > Allergy Parent of Allergy Children correlation.

    I might add that her 3 Children should strongly look into Allergy Testing and Immuno-Allergy DROPs.

    65% of ALL Asthma = Allergic Asthma.

    Asthma = migration of Allergy March to Allergic Asthma.

    ASTHMA ATTACKs = Enviro Allergy Triggers ( usually exacerbated by Enviro irritants ).

    If you have Allergic ASTHMA …
    and are NOT Neutralizing the Source of your Allergy Disease with Custom Formulated Immuno-Allergy DROPs ..

    Is like…

    “Trying” to put a Gasoline / Asthma Attack FIRE Out…

    But the Gasoline / Enviro Allergy Triggers Hose are STILL Pumping Gas.

    STOP a Lifetime Consumption of Medicating SYMPTOMs !

    It is Never to Late to STOP the Progression of Allergies in your Child.

    Visit your Primary Care Dr. and > DropYourAllergies.com

    Best Health = Wealth Regards,

    Stephen

    PS > Regarding CAP’s > This is just how I write.

  6. #6 Calli Arcale
    March 2, 2010

    All the people with asthma and allergies in my family (including yours truly) were vaginally delivered. My two children (born via c-section) have yet to develop significant allergies, though #2 shows some signs of seasonal allergic rhinitis. I have two cousins born via c-section; one has allergies. My family is a rather small sample size, and there is probably a genetic predisposition at work, but this small uncontrolled sample does not support the hypothesis.

    Honestly, I think there are too many confounders. It has good plausibility, but plausibility isn’t everything. And there are other studies which suggest that it doesn’t much matter where a baby gets their fecal flora — within a couple of months, it’s completely changed anyway.

    My biggest concern, though, is that people might take the advice to go ahead and universally dose with probiotics on the assumption that this might provide some benefit. The evidence is poor, and there are some very major problems with the plausibility of probiotics. While the *principle* is plausible, it’s worth looking at the actual pills sold in stores. A normal gut flora is a diverse ecosystem. Probiotics are usually less than half a dozen species of bacterium. I’ve heard this compared to repopulating a slashed-and-burned rainforest by planting corn. It’s not effective ecology at the macro scale, and probably isn’t at the micro scale either. So that’s one problem. The other problem is that there’s very little evidence the pills even work to establish the bacteria in your system. Some researchers have purchased off-the-shelf probiotics, tested them, and found that many did not even contain any live bacteria. (They attempted to culture them from the pills.) Yogurt is far more likely to contain live bacteria, but again, is it going to be helpful? And do the bacteria even gain a foothold against the existing strains? This is not clear, and at best, what you’ve described only addresses plausibility. It doesn’t address whether the theory is valid, nor clinical effectiveness.

    I’m not going to rush out and spend money on completely unquantified and largely unregulated medications because of the plausibility of the hygiene hypothesis. I think it’s still too big a leap.

    And I’m certainly not going to visit a fellow like Stephen who apparently thinks that making himself sound like Robert E McElwaine is the right way to use the English language.

  7. #7 Stephen
    March 3, 2010

    My Mother has ASTHMA.

    I have BAD Allergies .. maybe even Asthma.

    Now.. I’m see’ing the Same Symptoms in my Child.

    That is just not Acceptable.

    What can I do NOW to STOP my Child from suffering… as I have from Allergies / Allergic Asthma ?

    While there is no Cure for Allergic ASTHMA > Early Allergy Blood Testing and ImmunoTherapy Measures can be taken to Neutralize the Progression of Child’s Allergy MARCH to possibly Allergic ASTHMA.

    The Golden Window of Treatment = Age 6 mo. – 6 Yr > After that …Achoo & Ouch !

    It is never to late to Take Allergies out of your Child’s Future.

    Some C-Section / Probiotic Thoughts for Reader consideration.

    January 2009: According to a recent study from the University and the University Central Hospital of Helsinki, Finland, no allergy-preventive effect is extended to age 5 years by prenatal supplementation with probiotics in babies at risk for developing allergies; protection is conferred only to Cesarean section babies.

    Childhood allergies have increased significantly in industrialized countries during the past few decades. Researchers theorize that this rising incidence is the result of a lowered exposure to bacteria in early childhood.

    This exposure to microbes appears to be essential in jump-starting the immune system to develop healthy pathways that do not result in allergic conditions.

    Additionally, it’s been observed that infants who develop allergies have intestinal bacteria that are distinctly different from those of non-allergic infants, suggesting that the type of intestinal microflora is an important factor in forming allergic conditions.

    In a study published in the Journal of Allergy and Clinical Immunology (online January 2009) researchers from the University and University Central Hospital of Helsinki conducted a clinical trial of more than 1200 mothers whose infants would be at high risk to develop allergies. During the last month of their pregnancies, the mothers took daily doses of a probiotic mixture or a placebo, and their infants were given the same probiotic mixture plus a prebiotic or a placebo for the first 6 months of their lives. The children were followed for 5 years and evaluated for incidence of allergic diseases.

    The authors found that the frequencies of allergic and IgE-associated allergic disease and sensitization were similar in the children who had received probiotic and those who’d gotten placebo. Although there appeared to be a preventive effect at age 2, there was none noted at age 5. Interestingly, in babies born by cesarean section, the researchers found less IgE-associated allergic disease in those who had received the probiotic.

    “No allergy-preventive effect is extended to age 5 years by perinatal supplementation with probiotics in babies at risk for developing allergies; protection is conferred only to C-section babies”, says Dr. Mikael Kuitunen from the University Central Hospital of Helsinki. “However, it is possible that stronger and longer stimulation of the infant immune system possibly by varying the strains of bacteria, may result in better allergy-preventive effects.”

  8. #8 LadyShea
    March 5, 2010

    Interesting reading Tara.

  9. #9 Michelle Ziegler
    March 8, 2010

    When thinking about bacterial colonization of newborns, whether or not the infants were fed breast milk or formula should also be factored in. Breast milk can foster the growth of good bacteria and inhibit harmful bacteria in an infants gut.

  10. #10 shac
    March 10, 2010

    My friend has told me that almost all middle class and upper class Chinese have c-sections. That would be and interesting study. And I think almost none breast feed.

    When I was on inhalers for my asthma, it killed the flora in my mouth and I got a yeast infection in my mouth. For someone that regularly uses inhalers I would be concerned they are regularly compromising their flora. Also when I was on antibiotics while breast feeding my daughter got a yeast infection in her mouth. It took a very long time to go away (even with medication), so I think it took a long time for her flora to return to normal. But she doesn’t have asthma. I’m just saying our natural flora is important, but it doesn’t necessarily return to normal quickly especially after antibiotics or asthma medicine.

  11. #11 Calli Arcale
    March 12, 2010

    If you are well-off in China, you indeed do not breast feed — but your infant still gets breastmilk. It is considered fashionable to use a wet nurse. (The wet nurse’s child, however, will inevitably wind up on formula. Few lower-class Chinese can afford the time to nurse their child. The situation is complex, and influenced by both the One Child Policy and the near complete lack of worker protections.) So there are a lot of interesting situations for research there.

  12. #12 davidp
    April 9, 2010

    I’m a bit late for commenting on this as an assignment, but I found it well written and appreciate it being well referenced. As a blog it would be nice to have links to the papers where possible, rather than just referencfe details.

    Two obvious confounding factors with the C-section – Asthma link are that many C-sections (but not all) are due to serious risk factors or pre-birth problems for mother or child, and many are significantly before term as a result. I do not know how this can be excluded, especially since my personal experience is that the reasons given on the hospital forms are not always accurate (one of my wife’s was documented as due to a prior ceasarean, but in fact was due to a prior unexplained death of a healthy baby in early labour). A good start would be to analyse asthma for what appear to be elective caesarean’s within 1 week of term without special neonatal care requirements, and compare that with an equivalent group of vaginally delivered babies.

    I wholeheartedly agree that an RCT of probiotics with babies delivered by C-section would be the way to find out more. Exclusion of differences in breast fed v.s. formula fed as a factor would also be useful, as “2nd Year Medical Student” mentions.

  13. #13 BuckyBison
    April 14, 2010

    Has any study related asthma occurrence to “time to full term?” Since the fetus signals its lungs are ready by triggering pitocin release in the mother, I imagine the farther in front of “full term” the c-section is, the less developed the baby’s pulmonary system is. This may work in concert with the immune system/allergy theories put forward.

  14. #14 sesli chat
    April 24, 2010

    If you are well-off in China, you indeed do not breast feed — but your infant still gets breastmilk. It is considered fashionable to use a wet nurse. (The wet nurse’s child, however, will inevitably wind up on formula. Few lower-class Chinese can afford the time to nurse their child. The situation is complex, and influenced by both the One Child Policy and the near complete lack of worker protections.) So there are a lot of interesting situations for research there…