Science

Josef Neu, MD and Jona Rushing, MD

In the United States the rate of cesarean delivery (CD) has risen 48% since 1996, reaching a level of 31.8% in 2007. This trend is reflected in many parts of the world, with the most populous country in the world, China, approaching 50% and some private clinics in Brazil approaching 80%. While a significant number of CD are preformed for obstetrical indications, some are simply due to maternal request and may incur several risks for the child. Well known among these risks are neonatal depression due to general anesthesia, fetal injury during hysterotomy and/or delivery, increased likelihood of respiratory distress even at term, and breastfeeding complications. Concurrent with the trend of increasing CD, there has been an epidemic of both autoimmune diseases such as type 1 diabetes, Crohn’s disease, and multiple sclerosis and allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. The occurrence of these diseases is higher in more affluent, Western, industrialized countries. Several theories have emerged that suggest environmental influences are contributing to this phenomenon. Most notably, the “hygiene hypothesis” suggests that an overly clean environment, especially in early childhood, may contribute to the development of several childhood diseases. It was first proposed by Strachan, who observed an inverse correlation between hay fever and the number of older siblings. This was subsequently extended by others from the allergies to autoimmune diseases such as type 1 diabetes. Whether the increase in CD incidence is also causally related will be addressed in this review.
The interplay between the emerging microbial ecology of the gastrointestinal tract and the developing mucosal immune system serves as a backdrop for a relationship between CD and the emergence of some of these diseases. With the highly immunoreactive intestine serving as the largest surface area of the body that is exposed to the environment, especially a vast array of luminal microbes and antigens, it is intriguing to speculate that the intestinal environmental interaction during early development of the immune system may relate to these diseases. One intriguing component of this relates to the early development of the intestinal microbiota, the developing immune system and the early influence of cesarean versus vaginal delivery (VD) on these phenomena. The immune system undergoes major development during infancy and is highly related to the microbes that colonize the intestinal tract. It has been suggested that different initial exposures depend on mode of delivery (VD vs. CD). The microbes that “seed’ the intestine during either CD or VD may lead to changes in long term colonization and subsequent altering of immune development (Fig. 1). Here we will provide background about the human microbiota, its relationship to the developing immune system, and the relationship of mode of delivery on the colonization of the infant intestine, development of the immune system, and subsequent childhood allergies, asthma and autoimmune diseases.