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.
In the past decades, the incidence of cesarean delivery (CD) increased annually by 4%, and is highly variable geographically, ranging from less than 5% of deliveries in southern Africa to almost 60% in some parts of Latin America. In the US, the cesarean section rate has increased from 4.5%, in 1965, to 32.8% in 2010 and 2011, and, thus, nearly one mother in three now gives birth by cesarean section.
The American College of Obstetricians and the Society for Maternal-Fetal Medicine released new guidelines, relevant mostly for first-time mothers that are aimed at safe prevention of the primary cesarean delivery.
Epidemiological studies indicate that elective cesarean section (CS) is linked to a greater risk of developing immune diseases such as asthma, allergies, type 1 diabetes, and celiac disease and also obesity or attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD).
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”.
In an elegant recent review, Roberto Romero and Steven Korzeniewski summarize the three major mechanisms that may drive the short- and long-term consequences of cesarean delivery on the immune system, and the differences between normal delivery and the cesarean section.
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.
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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.
In 2022, Ayya Keshet and colleagues, in a study published in PLOS One, utilized data from electronic health records of 737,904 births and estimated the effect of cesarean delivery on predefined long-term pediatric outcomes.
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.
