The epigenetic jury is still out on C-sections

A new scientific field investigates delivery methods

The epigenetic jury is still out on C-sections
Nurses and midwives across the world are studying whether delivery practices affect babies’ DNA. [Image Credit: BigStockPhoto.com]
By | Posted June 12, 2012
Posted in: Life Science
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Thinking his wife and unborn child would die, Dr. Jesse Bennett performed the first successful reported cesarean section on American soil in 1794. Then, for good measure, he removed her ovaries so he (yes, he) “would not be subjected to such an ordeal again.”

Unbeknownst to Bennett, giving his wife a C-section might have affected their daughter’s DNA, her children’s and her grandchildren’s. People typically think about life as nature versus nurture — our genes versus our environment. But what if the environment, or our grandparents’ environments, shaped our genomes literally at the moment of birth?

Many people know the genome is not immune to environmental forces. A nuclear bomb can mutate DNA. A retrovirus like HIV can incorporate itself into genetic code. But what about subtler events? Scientists are beginning to learn how certain twists and trials, such as famine or stress, might influence which genes in our DNA are switched on or off.

Having a C-section, a group of nurses and midwives are now suggesting, could possibly be one of those twists. They are both eagerly and carefully launching studies to examine possible connections between C-sections and medical conditions. The idea is controversial, unproven and has many skeptics, but birth experts say that studying C-sections’ effects on infants and their descendents is an important question that requires experimental testing.

Every cell in the body has the same DNA. Environmental influences, however, may put chemical tags on DNA, silencing one gene or boosting another.

It’s possible Elizabeth Bennett’s C-section — a sudden environmental event — changed how her daughter’s genes were expressed. It’s also possible that her daughter passed these environmentally-influenced switches on to her descendents. The study of passing on these environmental switches is called epigenetics.

Epigenetics is beyond genetics — epi meaning ‘above’ or ‘upon.’ Cancer researchers have studied it since the 1990s, and scientists in other fields are examining the long- and short-term effects environmental markers can have on our genes. Now a group of medical professionals are comparing vaginal births to C-sections.

For many nurses and midwives, it’s about time the medical community focused on the potential environmental markers a C-section could impart on a child’s genome. In January, 11 women from the US, the UK and Australia gathered in Hawaii for a panel investigating the epigenetics of birth.

“The clinical and scientific community have paid attention to the critical time period of gestation and early life, but have not considered labor and birth as a sensitive period whereby epigenetic modulation can occur,” Aleeca Bell, one of the panel’s speakers and an assistant professor of nursing at the University of Illinois, Chicago, wrote in an email.

Since Bennett’s first daring surgery, C-sections have steadily increased. In 1997, physicians delivered about 20 percent of all births in the U.S. by C-section. In 2007, just 10 years later, C-sections accounted for 31 percent of American births.

Some C-sections are medically necessary for mothers, such as in cases of preeclampsia or gestational diabetes. But elective C-sections are increasing, according to a 2005 federal government study that took population growth into account. About 20 percent of C-sections were elective in 1994. That number rose to 28 percent in 2001, an increase of about 40 percent.

Elective C-sections could be putting the infant at unnecessary risk, says the group of midwives and nurses who held the epigenetics panel. If — and it’s still a big if — researchers do find C-sections have potentially harmful effects for the child, it could change the way families and physicians view the operation.

Hannah Dahlen, an Australian midwife, says it could increase respect and demand for vaginal birth. “We’re at the beginning of a very exciting time,” Dahlen says. “I think in 10 years we will potentially look back at what we are doing now and think, ‘What on earth did we do?’”

Dahlen helped spearhead the Epigenetic Influence and Impact on Childbirth meeting. She has practiced midwifery for 24 years, recommending vaginal birth in a country with a 30 percent C-section rate. In 2010, she convened with her colleagues at the annual Royal College of Midwives conference in England.

They were all frustrated “that despite the research, political activism and efforts they and many others were putting in to increase the rate of normal birth, intervention during childbirth kept rising and arguments about safety and outcomes all had a short term focus,” she wrote in an email.

The women were familiar with epigenetics, and wondered if it might provide a new lens they could use to study and compare vaginal birth to C-section delivery. “We thought, let’s change the track and let’s start a new song,” Dahlen says.

The difficulty with studying the effects of birth methods is that studies tend to be observational — meaning that women are allowed to choose their own method of giving birth. The gold standard of medical research is the randomized study, but it is not considered ethical or feasible to randomly assign women to have C-sections or vaginal births. This means that there will always be doubt as to whether associations are related to the birth method itself or other traits that people who choose one birth method over another share.

However, observational studies have provided clues to correlations between birth method and health risks. In recent years, they have indicated that infants born by C-section appear to have an increased risk for asthma and allergies, Type 1 diabetes, childhood leukemia and testicular cancer. In a 2011 study, researchers found that girls born via C-section may be at a higher risk for developing multiple sclerosis later in life.

The mechanism for developing these diseases is unknown, but Swedish scientist Titus Schlinzig suspects epigenetics, he co-wrote in a 2009 study.

That paper was the first to link C-sections to possible epigenetic effects. Schlinzig and his colleagues looked at 21 vaginal births and 16 elective C-sections. They took two blood samples, one from the umbilical cord after birth and a second sample three to five days following birth. Then they studied a keystone of epigenetics: DNA methylation.

DNA methylation is associated with the silencing of genes. When a methyl group — a carbon atom with three hydrogen atoms — attaches to a cytosine base, one of the four building blocks of genes, it puts the gene out of commission.

In the study, Schlinzig’s group looked at DNA methylation in white blood cells. It found that infants born by C-section had more DNA methylation in their white blood cells than babies delivered vaginally. After three to five days, methylation decreased in the C-section babies, and the two groups were no longer significantly different.

In its conclusion, Schlinzig’s group wrote that it was unknown if the effects from the high DNA methylation rate in C-section infants were long lasting, but said it highlights a new area of clinical research that could have important health implications.

Scientists can’t say for sure that DNA methylation leads to gene silencing, but it has a strong correlation, says Joyce Ohm, a professor of biochemistry and molecular biology at the University of North Dakota School of Medicine

Intrigued by the Schlinzig study, the women organized the epigenetics panel. There, they co-wrote a paper about potential issues surrounding the epigenetics of birth, began creating a website as a hub for like-minded researchers and left with research projects up their sleeves for the coming years.

Panel speaker Bell plans to study how synthetic oxytocin given to women during labor might have an epigenetic effect. “We know oxytocin promotes positive mood and social behaviors while helping to lower stress,” she wrote in an email. With so many women and infants exposed to synthetic oxytocin at birth, as well as labor pain medication, the medical field should learn if it has any effect on human epigenetics, she wrote.

Studying the epigenetics of birth is a hot topic, says Louis Muglia, the director of the Center for Prevention of Preterm Birth at Cincinnati Children’s Hospital Medical Center. It makes sense that the fetus would prime itself for life during gestation, he says. English geneticist Marcus Pembrey, the father of trans-generational epigenetics, shone light on the concept after researching the people of Overkalix, an isolated Swedish community.

In the 1800s, Overkalix’s residents depended heavily on farmers. Pembrey and his colleagues had access to records about the community’s feasts, famines and death certificates, and pieced together data for a landmark 2006 study: If a grandfather lived during a famine, his grandson was four times as likely to die of diabetes than if he lived during a time of plenty. Somehow, the grandfather’s genes were switched on or off, helping his body conserve calories — switches that were passed down to his grandson. If the grandson had access to too much food, he could get diabetes and die.

Studying the epigenetics of birth is “intriguing,” Muglia says, adding he wants to wait for the results before jumping on the bandwagon.

In context, birth is a relatively short life event. “You wouldn’t want the body to be reprogramming itself every time an event came up,” Muglia says. “To me it’s a little counterintuitive that the labor process would have as big an impact on epigenetic programming as pregnancy.”

Short window or not, Bell says birth deserves to be studied from an epigenetic standpoint, though it will take a few years to accrue preliminary data. “As midwife researchers, we view labor and birth as a time when small physiological changes can have enormous impact on the mother and infant,” she wrote in an email. “Epigenetics may be a useful tool in discovering how.”

Whatever Bell and her colleagues find, it will take a while to sort out. First, researchers will have to follow generations of babies. Historians did not follow Bennett’s daughter, so it is unknown if she developed any impairments. What is likely is this: If she had children of her own, she probably delivered them vaginally, the most common method in the early 1800s. This normal birthing process is exactly what the nurses and midwives support. But they’ll have to wait for the data before they can reveal any secrets hidden in the epigenome.

Posted in: Life Science

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  1. C/sections are definitely a case of social engineering. It’s about the imprinting process. Just think of a school where 80% of the students were delivered by C/section.( this is a true example) These children have not been born they have been delivered. How can anybody think that they will be the same as students from a school where 80% were born drug free by their own efforts? (an imagined sample as they are impossible to find)
    How can a baby subjected to multiple doses of ultra sound in utero be considered the same as a baby whose cells have been spared such invasive procedures.
    It’s not rocket science it’s common sense of which there is a great shortage in this area.

    Rachana Shivam, June 13, 2012 at 3:09 am
  2. Sounds like yet another way to make mothers feel guilty if for any reason they have a C-section.

    Puanani Frobel, June 13, 2012 at 6:12 pm
  3. This study is already flawed because of the bias of those undertaking it: midwives. Midwives have a vested interest in promoting the Midwifery Model of Birth which privileges “normal” vaginal birth as superior to C sections. Naturally, they are going to see the children born via surgical procedure as somehow genetically defective compared with those born “naturally.” The same with newborns exposed to oxytocin and epidurals during medicated vaginal deliveries.

    It is pretty clear that because their viewpoints have not been accepted by the wider world they are turning to epigenetics in hopes of gaining some “scientific” credibility.

    Schlinzig’s study showed a tiny difference that disappeared by the time the newborns were a few days old. The Pembry study definitely showed significant effect of a major event on future generations. But there is a huge difference between a quick surgical procedure and a long lasting famine. Maybe instead of wasting research dollars on the unlikely long term effects of C sections, money should be spent on looking at how to counter the effects of actual traumatic events like starvation, war, and abandonment on infants.

    Sara Savel, June 13, 2012 at 8:24 pm
  4. So – - – if the stress of c- section causes changes in the infant’s DNA, why wouldn’t the stress of birth do the same thing?

    MonaSw, June 13, 2012 at 11:09 pm
  5. Follow the money!

    Midwives cannot make money from C-sections, so they demonize them. There is precisely ZERO evidence of any epigenetic effects of C-section. Moreover, none of the midwives on the panel have any background or training in epigenetics and are therefore not qualified to assess the possibility of an epigenetic impact.

    Curiously, the panel never bothered to consider if oxygen deprivation during labor (a major indication for C-section) has any epigenetic effects.

    Midwives prefer whatever they can charge for and demonize everything else. This is just a particularly unethical method of drumming up more business.

    Amy Tuteur, MD, June 14, 2012 at 9:55 am
  6. This sentence is incorrect: ” C-sections are medically necessary for mothers, such as in cases of preeclampsia or gestational diabetes.”

    A C-Section is not medically necessary in either scenario. Plenty of woman can have easy vaginal births with both conditions.

    There are very few scenarios in which a C-section is TRULY medically necessary, namely complete placenta previa or placental abruption, transverse lie, cord prolapse and true cephalo-pelvic disproportionment (which is exceptionally rare).

    Sarah, June 14, 2012 at 10:45 am
  7. Fascinating. The exact link might not be understood yet, but just because they haven’t figured it all out doesn’t mean it’s not there. We used to not understand the implications of early cord clamping either, but now science is showing us how important it is to delay clamping. I think it’s reasonable to wonder if we might see something similar here.

    One Birth, June 15, 2012 at 11:01 am
  8. Follow the money, indeed! I believe most OBs make some of that and I don’t begrudge them their compensation. But midwives–not OBs–are the guardians of normal labor and birth. I agree wholeheartedly with Sarah, commenter #6. At no other point in history have c-sections been at such a high rate, with no commensurate improvement to either baby or mama. Reasons such as the birth taking “too long” or doctors suspecting the baby might be “too big” or a baby that goes beyond it’s due date are the top reasons given for c-sections in my metropolitan area, and these are not good indications for major surgery. Although c-sections can be life-saving for mothers and babies *when done in true emergency situations*, those situations are rare–nowhere near 35% of births in my city. It would seem that the more this surgery is perfected, the “safer” it becomes, and the more (over)used it is. What a shame.

    Lisa, June 15, 2012 at 7:58 pm
  9. Amy Tuteur – your comment is actually quite funny considering you are an OB and you yourself want to demonize normal vaginal birth! FOLLOW THE MONEY indeed! You make a lot more money from C sections so it just goes to show that you want this new field of research to be unfounded! Unethical?!! I think moreso the fact that you continually undermine midwives and their considerable skill and knowledge they have to offer!

    Carley Valikoula, June 15, 2012 at 8:15 pm
  10. Sorry, but I highly doubt that the midwives on this panel are going to these great lengths to get more money by increasing the vaginal birth rate. That’s just not a reasonable assumption. Yes, midwives are huge supporters of vaginal birth and in fact YES, in many cases cesarean sections are made by a hasty medical judgement. Unfortunately many medical decisions in obstetrics today are driven by malpractice lawsuits. Cesareans are a quick way to avoid getting sued. I don’t blame MD’s, it’s a whole system that has cause a great downward spiral.

    The World Health Organization believes a reasonable cesarean rate is around 15% and it is nearly 33% in the United States. We HAVE to start asking ourselves why and how we have gotten so far off course. I think this study is a great start to opening our minds to the long-term impact of cesarean sections. This may help decrease the elective cesarean rate or encourage providers to allow women to labor longer before jumping to the cephalopelvic disproportion diagnosis. We owe it to our women and our future generations.

    Amber Critchfield, June 15, 2012 at 10:58 pm
  11. I had Placenta Previa with my daughter and therefore had a C-Section 9 years ago. She was diagnosed with Type 1 diabetes 3 years ago. I am currently 7 months pregnant and hoping for a VBAC – hopefully avoid any C-Section complications – if that is the connection…

    Debbie, June 17, 2012 at 12:27 pm
  12. Insurance companies, both health and malpractice, are the number one reason why C-sections exist. Doctors are afraid of being sued, and healthcare coverage encourages expeditious procedures, so the deck is stacked before the notion of “best practices” even enters the delivery room. The observational data above should therefore be overlaid with data about patient coverage and physician malpractice premiums as well as physician malpractice claims before assigning a reason for the increase.

    Cathy Finn-Derecki, June 18, 2012 at 9:32 am
  13. “They were all frustrated “that despite the research, political activism and efforts they and many others were putting in to increase the rate of normal birth, intervention during childbirth kept rising and arguments about safety and outcomes all had a short term focus,” she wrote in an email.”

    Thanks, Dr. Dahlen, for actually admitting that the most damning indictment of midwives is true: they are more concerned with preventing C-sections than preventing perinatal death (short term focus).

    That’s what happens when you think process is more important than outcome.

    Hannah Dahlen, and the rest of the midwives should be ashamed of themselves that they don’t care whether babies live or die so long as they can preside over vaginal births.

    PS: The World Health Organization withdrew their recommendation several years ago, acknowledging that there had NEVER been any evidence to support an optimal rate less than 15%.

    Amy Tuteur, MD, June 18, 2012 at 9:48 am
  14. interesting….. i read more mothers and babies die from casarean complications than from the numerous fabricated vaginal birth complications

    Diceman, July 24, 2012 at 8:49 pm
  15. Is it the C-section or the drugs (epidural) that cause the methylation? I had gestational diabetes and everything went well towards a vaginal delivery when my baby had suffering for the cord on her neck (5 turns) and I was very happy I got a C-section AND my baby!

    Zaida, July 25, 2012 at 4:58 am
  16. It is so easy to have an opinion people! But when you have a personal connection – like 1 of your 4 children has diabetes and he was the only one among them born by c-section – it gets real! 20% higher incidence in those born by c section? THAT IS MAJOR. Diabetes is a terrible thing. I am horrified by how many people are dismissing further investigation in that context.

    Lavinia, October 24, 2012 at 5:19 am
  17. Why is anyone attacking midwives for saying this area of study is important? In the UK they carry out most of the prenatal care, whatever way your child ends up being born, and in hospital they again help new mothers look after newborns whatever way they were born. They must see issues first hand that have given them cause for concern. If they did not raise concerns where they had them, wouldn’t we accuse them of professional negligence?

    Colin, October 24, 2012 at 5:24 am
  18. Broads are squeezing out babies the size of toddlers. Babies used to weigh 7 pounds.

    Childfree by Choice, January 22, 2013 at 11:38 am
  19. Bias does not have to be malicious to be harmful. Any harm may only extend to misunderstanding.

    Midwives have a vested interest in handling deliveries. That does not make them wrong.

    Midwives should be upfront about possible bias, especially with themselves.

    Bob, February 25, 2013 at 1:01 pm
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