Planned C-sections linked to increased risk of childhood leukemia, study finds

Children born by planned cesarean section are 21% more likely to develop acute lymphoblastic leukemia (ALL), a childhood cancer, than those born vaginally, a new study finds.

The research, conducted in Sweden, is consistent with previous studies that also found a link between pediatric ALL risk and C-sections. More recent research, including this latest study, has specifically connected the majority of that risk to planned C-sections. In this study, planned C-sections were defined as those initiated prior to labor.

But crucially, the risk of ALL, and childhood cancer in general, remains low across the board, said Joseph Wiemels, a professor of population and public health sciences at the University of Southern California who was not involved in the work. In the U.S., about 4.8 in 100,000 children are diagnosed with leukemia per year. So while "the relative risk [for ALL] is significantly higher" for babies born by planned cesarean, Wiemels cautioned that that the risk is "still relatively low" overall.

Cesarean section "is a vital and often life-saving component of modern obstetric care," lead study author Christina Evmorfia-Kampitsi, a postdoctoral researcher at Karolina Institutet, told Live Science in an email. Some people give birth by planned C-section due to maternal conditions, such as preeclampsia, or to protect the baby's health because they aren't getting enough oxygen, for example.

"Our findings should not be a cause for concern when the procedure is medically indicated," Evmorfia-Kampitsi said.

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Confirming a known link

What's unique about the study, published July 4 in the International Journal of Cancer, is that researchers controlled for a range of characteristics in mothers and newborns and still found a higher risk of ALL in children born by planned cesarean.

"Thanks to the richness of Swedish register data, we were able to adjust for a wide range of maternal, pregnancy, and neonatal [newborn] factors," Evmorfia-Kampitsi said. "This helps strengthen the evidence that the association is not merely due to underlying conditions that might have led to the CS [C-section] in the first place."

Controlling for these other factors is important, Wiemels said, in part because maternal ages above 35 are also associated with a higher risk of children developing ALL. There's also a link between birth defects and ALL risk, as well as environmental factors like radiation. But because ALL occurs at such young ages, researchers have been exploring factors before and just after birth that may lead to its development, Dr. Danielle Daee, program director of the genomic epidemiology branch at the National Cancer Institute who wasn't involved in the work, told Live Science in an email.

For the study, researchers looked at the mode of delivery — vaginal, planned cesarean or unplanned cesarean — in more than 2.4 million births that took place in Sweden over 20 years. Data on newborns' weights, birth defects, and whether their mothers were overweight or had obesity, diabetes or preeclampsia were also examined. Additionally, they looked at the incidence of ALL among these children over time.

The researchers also grouped the kids based on the decade in which they were born, to account for changes in obstetric practice, the rate of C-sections, changes in how childhood cancers are diagnosed, and other factors that might vary over time, Evmorfia-Kampitsi said.

More than 375,000 of the children, about 15%, were born by C-section, including about 213,000 planned, which were initiated prior to labor starting. About 1,200 of the 2.4 million children, or 0.05%, developed ALL.

The risk of ALL was higher among the babies born by any type of C-section than among those born vaginally. There was a slight increase in risk tied to unplanned C-sections, which began post-labor, but the risk was highest among those born by planned cesarean, initiated before labor began.

The planned C-sections could be further divided into "planned" and "acute," with the latter meaning there was some sort of immediate medical need, like fetal distress. These acute cases didn't seem tied to any increase in cancer risk — but because there were only a handful of such cases, it's difficult to draw firm conclusions.

“These results should be interpreted with caution," Evmorfia-Kampitsi said. "Our primary finding remains the increased risk associated with planned pre-labor CS."

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Cause for concern?

Childhood ALL is most often diagnosed in children under 5 years old, and the study findings were only statistically significant for the children in this age group. In other words, the connection between planned C-sections and ALL seems clearest in that age range, Evmorfia-Kampitsi said.

The study may "tell us something about leukemia risk, and the mechanisms behind that risk," Wiemels suggested.

On that front, it's known that there are genetic mutations that can develop before birth and cause children to be born with pre-leukemia cells. However, more children are born with these cells than actually develop full-blown cancer, said Erin Marcotte, an associate professor in the Division of Pediatric Epidemiology & Clinical Research at the University of Minnesota, who wasn't involved in the new study.

"It's likely that most children are able to cull those cells," Marcotte told Live Science in an email. But how?

There are two leading theories as to how this works, and how those mechanisms may be compromised by planned C-sections. The first suggests that babies born via C-section miss out on exposure to microbes in the vaginal canal, which may promote a more "permissive" environment for leukemia to develop, Wiemels said. Babies born via C-sections that begin before labor are exposed to fewer microbes than those whose C-section start after labor because, at that point, the water has broken.

The second hypothesis is that babies born by planned C-section miss out on short-term exposure to stress hormones that they would typically encounter during labor. It's thought that these hormones may help eliminate pre-leukemia cells.

Adding to the idea is the fact that corticosteroids are a mainstay of childhood leukemia treatments, and are similar to body-made cortisol. Additionally, Kjeld Schmiegelow, a clinical professor at the University of Copenhagen, has hypothesized that the stress that stems from infections in early childhood can help eliminate pre-leukemic cells.

Whatever the root cause of the link, the absolute risk of ALL remains low even in the context of C-sections. But it's potentially something for doctors to consider, Evmorfia-Kampitsi said. "When a CS is being considered without a clear medical indication, it's important to be aware of potential long-term outcomes," she said.

Still, more research on the relationship between ALL and planned cesarean is needed, as countries with higher rates of cesarean deliveries don't always have higher rates of ALL. Since the study was done in Sweden, "it is plausible, but not confirmed, that other populations, with different demographic features and environmental exposures, may have a similar result," said Daee.