Cesarean section – increased risk for immune-related diseases
According to a study published in the journal Pediatrics, a research team from Denmark provides new evidence that the offspring of women who deliver by cesarean section may have an increased risk for certain immune-related diseases.
The American College of Obstetricians and the Society for Maternal-Fetal Medicinereleased new guidelines, relevant mostly for first-time mothers that are aimed at safe prevention of the primary cesarean delivery.
In the Pediatrics study, Astrid Sevelsted and colleagues from the University of Copenhagen & the Danish Pediatric Asthma Center, Copenhagen University Hospital, Copenhagen, Denmark collected data from 2 million full-term children born by cesarean section, as recorded in the Danish national registries between 1977 and 2012.
The authors of this study report that children delivered by cesarean section had significantly increased risk of asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies and leukemia. Of note, as per this study, type 1 diabetes, psoriasis, and celiac disease were not associated with cesarean delivery.
The study supports the hypothesis that the perinatal life is important for later development of chronic diseases. Sevelsted et al. discuss that the normal delivery canal exposes the child to a composite microbiome different from the one encountered during a cesarean delivery. Thus, the effect from cesarean delivery is mediated by “changes in the microbiome of the newborn”.
This includes “1) acquisition of an atypical microbiome at birth; 2) the effect of labor on the immune system; and 3) the development of memory of the first two events through epigenetic changes that modify the nature of the immune response and predispose to immune-related disorders” (after cesarean section).
The authors of this review also discuss recent data indicating that autism, type II diabetes, inflammatory bowel disease and gastric cancer have been associated with changes in the intestinal microbiota, and/or the susceptibility to influenza, retrovirus transmission, and colon cancer. Thus, all this supporting that microbial colonization of the gastrointestinal and respiratory tract in the perinatal period have an important role in the development of mucosal homeostasis and in the predisposition to chronic inflammation.
Interestingly, maternal overweight, which often results in cesarean delivery, is a strong risk factor for child overweight. But little is known about the joint contribution of birth mode and microbiota in the infant gut to the association between maternal prepregnancy overweight and child overweight.
In 2018, Hein M. Tun et al., in a study published in JAMA Pediatrics, demonstrated that infants born vaginally to overweight or obese mothers were 3 times more likely to become overweight at age 1 year, while cesarean-delivered infants of overweight mothers had a 5-fold risk of overweight at age 1 year. Thus, in a general population birth cohort of 935 infants, those born to overweight or obese (OWOB) mothers were more likely to develop OWOB at ages 1 and 3 years, and the magnitude of the risk varied by birth mode.
Of note, according to authors of this study, multiple mediator path modeling revealed that birth mode and infant gut microbiota (Firmicutes species richness, especially of the Lachnospiraceae family) sequentially mediated the association between maternal prepregnancy overweight and childhood overweight at ages 1 and 3 years. Thus, the authors believe that both maternal weight status and cesarean delivery shape early-life gut microbial development and the weight outcome of offspring, for which a mediation role for gut microbiota has been posited.
The authors found that cesarean delivery CD had an effect on the occurrence of asthma, and may also have an effect on atopy, allergy and the number of respiratory infection events by the age of 5 years. Among all pediatric outcomes analysed, cesarean delivery had the largest effect on atopy and asthma development. The study may pave the way to future research on the mechanism underlying these effects and possible intervention strategies targeting them.