The increased prevalence of autoimmune diseases such as type I diabetes, allergic diseases such as asthma and inflammatory bowel diseases such as Crohn’s disease have all been linked to improved hygiene taking place during recent decades in westernised societies. Several experimental and follow-up studies suggest that early gut microbiota play a crucial role in the development of the immune system and early deviations in the gut microbiota may thus have long-term pathological consequences.
Children delivered by Caesarean section have been demonstrated to have aberrant gut microbiota changes possibly extending far beyond infancy. These children also possess an increased risk of allergic sensitisation and allergic respiratory diseases suggesting a major impact of mode of delivery on the developing immune system.
Vaginally delivered neonates have significantly higher counts of leucocytes and neutrophils in blood than those delivered by Caesarean. This difference does not extend beyond the neonatal period, whereas phagocyte functions seem to be altered at least for the first 6 months of life. A large study of over 8000 umbilical cord blood samples, all banked for future umbilical cord blood transplantation, demonstrated decreased percentages of helper T, cytotoxic T and B lymphocytes and increased percentages of natural killer lymphocytes in cord blood of neonates born by Caesarean section compared with neonates delivered vaginally. In a population-based prospective cohort study of 571 neonates, however, only an independent decreasing effect of Caesarean delivery on absolute natural killer lymphocyte counts in cord blood was found. These changes are probably dependent on eg, stress-related factors associated with different types of delivery.
We have prospectively evaluated the effects of mode of delivery on humoral immunity in 165 children, of whom 141 were born by vaginal delivery and 24 by Caesarean section. Gut mucosal immunity was indirectly studied by ELISPOT assay. We found that children delivered by Caesarean section mounted a stronger non-specific humoral immune response during infancy measured by total numbers of IgA, IgG and IgM-secreting cells, whereas the antigen-specific immune response against milk antigens (casein and beta-lactoglobulin) remained unaltered. These differences possibly reflect excessive antigen exposure across the vulnerable gut barrier in Caesarean section infants.
Neonates born by Caesarean delivery seem to have alterations both in innate and adaptive immunity and at least some of the differences may extend beyond the neonatal period. Mode of delivery may also have long-term effects on the development of immunological diseases such as allergies. More large prospective well-conducted clinical follow-up studies are needed to address the question in detail in the future.