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Caesarean section linked to increased risk of acute lymphoblastic leukaemia

Jairia Dela Cruz
20 Apr 2018

Infants delivered via caesarean section may be at increased risk of developing acute lymphoblastic leukaemia (ALL), according to a US study. Altered microbiota colonization is a possible explanation for this risk, although clear biological mechanisms have yet to be established.

In a cohort of 443 infants diagnosed with acute leukaemia (including ALL and acute myelogenous leukaemia [AML]) and 324 healthy controls, multivariable logistic regression models revealed that caesarean delivery due to any indication was associated with an elevated risk of infant ALL (odds ratio [OR], 1.52; 95 percent CI, 1.02–2.25). No difference in risk was observed according to whether caesarean section was performed prelabour or as an emergency procedure. [Cancer Epidemiol Biomarkers Prev 2018;27;473-478]

On the other hand, neither prelabour nor emergency caesarean delivery was associated with AML (OR, 1.02; 95 percent CI, 0.64–1.62). Moreover, analyses stratified by MLL gene rearrangement status showed no significant associations between caesarean delivery and MLL-negative and MLL-positive leukaemia.

Associations between caesarean delivery and infant ALL remained significant in sensitivity analyses, excluding infants diagnosed at <3 months of age. The investigators noted that such infants might have compromised health at birth, which may confer an increased risk of foetal distress and other indications for birth by caesarean section.

The increased risk of infant ALL associated with caesarean birth may be attributed to altered microbiota colonization, the investigators pointed out, adding that a clear biological mechanism has yet to be established.

“Intestinal microbiota influence early postnatal immune development through interactions with intestinal Toll-like receptors and production of suppressive cytokines, transforming growth factor-β (TGF-β), and IL [interleukin]-10, which play a critical role in producing a balanced Th1 and Th2 immune response,” they explained.

Mode of birth has been reported to alter both composition and diversity of intestinal microbiota in humans. Microbiota colonization occurs during the first moments of life, and the said alterations persist through the first 6–12 months of life, a critical period for immune development. [Proc Natl Acad Sci USA 2010;107:11971-11975; Gut 2014;63:559-566]

Additionally, there is evidence suggesting that differential microbiota colonization may impact the risk of autoimmune disorders, chronic diseases, infection and many types of adult cancer. [Curr Allergy Asthma Rep 2012;12:511-519; Curr Opin Lipidol 2006;17:157-161; Annu Rev Immunol 2012;30:759-795; Nat Rev Cancer 2013;13:800-812]

Despite several strengths including the availability of medical records to validate self-reported mode of birth, the study had several limitations, the investigators acknowledged.

First, the control group might not be representative of the source population of cases with respect to exposure distribution as the study was case–control in design. Second, statistical power was not sufficient to assess the possibility of confounding by indication, given that some maternal or foetal pathology that increases risk of caesarean delivery also predisposes the infant to leukaemia.

“Future larger studies with detailed information on molecular subtype, including MLL rearrangement status, and indication for caesarean delivery will be important to further examine this association with enhanced statistical power,” the investigators said.

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