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Prelabor cesarean delivery may increase risk for childhood ALL
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Children delivered by prelabor cesarean section appeared at an increased risk for childhood acute lymphoblastic leukemia, according to the results of a pooled analysis.
However, this association did not persist for acute myeloid leukemia, nor for other cesarean birth methods, such as emergency cesarean delivery.
“Recently, several studies have indicated a higher risk for immune-related disorders — such as type 1 diabetes, asthma and allergies — among children born by cesarean delivery,” Erin L. Marcotte, PhD, MPH, assistant professor of pediatric epidemiology at University of Minnesota, told HemOnc Today. “There are few studies available on whether cesarean delivery impacts the risk for childhood leukemia, and they are generally limited by small sample sizes or inadequate information on mode of birth.”
Erin L. Marcotte
Marcotte and colleagues performed a pooled analysis of data from 13 case–control studies conducted in nine countries by the Childhood Leukemia International Consortium to evaluate any association between leukemia and cesarean delivery.
These studies included data from 8,780 children diagnosed with ALL, 1,332 children diagnosed with AML and 23,459 healthy controls aged 0 to 14 years and born between 1970 and 2013.
The researchers had access to delivery information from 99% of children with ALL (n = 8,655), 97% of children with AML (n = 1,292) and more than 99% of controls (n = 23,351).
Four studies had data regarding indications for cesarean delivery (ALL, n = 1,061; AML, n = 138; controls, n = 1,401).
Multivariable regression models adjusted for birthweight, age, sex, ethnicity, parental education, maternal age and study showed cesarean delivery due to any indication resulted in a slightly increased, although not statistically significant, risk for ALL (OR = 1.06; 95% CI, 0.99-1.13), mainly driven by the B-cell immunophenotype.
When researchers stratified data for indications that would have resulted in prelabor or emergency cesarean birth, prelabor cesarean delivery significantly increased risk for ALL (OR = 1.23; 95% CI, 1.04-1.47), whereas emergency cesarean did not (OR = 1.02; 95% CI, 0.81-1.3).
The risk for ALL associated with prelabor cesarean delivery appeared especially apparent among children aged 0 to 3 years (P = .0079). However, researchers observed no other subgroup associations.
The risk for AML did not increase with any indication of cesarean birth (all indications, OR = 0.99; 95% CI, 0.84-1.17; prelabor cesarean, OR = 0.83; 95% CI, 0.54-1.26; emergency cesarean, OR = 1.05; 95% CI, 0.63-1.77).
The researchers acknowledged study limitations, including the potential for control populations to not accurately represent leukemia cases.
“If future studies produce similar results, we will need to determine what is causing the association,” Marcotte said. “It is known that children born by prelabor cesarean delivery are exposed to significantly lower levels of stress hormones at birth. These hormones may have beneficial effects on babies' immune systems. Compounds similar to cortisol, the main stress hormone, are used to treat leukemia and there is some evidence that early exposure to high levels of cortisol may be beneficial.
“This research adds to the growing body of literature that suggests that there are harmful long-term effects of cesarean delivery,” Marcotte added. “Because cesarean rates have been increasing dramatically worldwide over the last several decades, our study may help to inform guidelines and policies to reduce these rates.”
More focused research is needed to definitively link birth methods to the risk for childhood ALL, Joseph L. Wiemels, PhD, associate professor of cancer epidemiology at University of California, San Francisco, and a Leukemia & Lymphoma Society clinical research scholar, and Xiaomei Ma, PhD, associate professor of chronic disease epidemiology at Yale School of Public Health, wrote in an accompanying editorial.
“As pointed out by the investigators, clinical practices regarding delivery vary widely around the world and within the specific countries included in this analysis,” Wiemels and Ma wrote. “Indeed, even in a single country (the USA), rates and reasons for cesarean delivery have fluctuated strikingly from the 1960s to now, along with the suggested benefits of vaginal birth. The report by Marcotte and colleagues suggests one further adverse outcome that might be reduced with a stressful vaginal exit from the womb. Since a biological explanation of the data in the Marcotte analysis is not yet possible, their report is probably not the last epidemiological statement on this subject, but rather a call for further research.” – by Cameron Kelsall
For more information:
Erin L. Marcotte, PhD, MPH, can be reached at marcotte@umn.edu.
Disclosure: The NCI provided funding for this study. The researchers, Wiemels and Ma report no relevant financial disclosures.
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