Childbirth and consequent atopic disease: emerging evidence on epigenetic effects based on the hygiene and EPIIC hypotheses

Abstract

BackgroundIn most high and middle income countries across the world, at least 1:4 women give birth by cesarean section. Rates of labour induction and augmentation are rising steeply; and in some countries up to 50 % of laboring women and newborns are given antibiotics. Governments and international agencies are increasingly concerned about the clinical, economic and psychosocial effects of these interventions.DiscussionThere is emerging evidence that certain intrapartum and early neonatal interventions might affect the neonatal immune response in the longer term, and perhaps trans-generationally. Two theories lead the debate in this area. Those aligned with the hygiene (or ‘Old Friends’) hypothesis have examined the effect of gut microbiome colonization secondary to mode of birth and intrapartum/neonatal pharmacological interventions on immune response and epigenetic phenomena. Those working with the EPIIC (Epigenetic Impact of Childbirth) hypothesis are concerned with the effects of eustress and dys-stress on the epigenome, secondary to mode of birth and labour interventions.SummaryThis paper examines the current and emerging findings relating to childbirth and atopic/autoimmune disease from the perspective of both theories, and proposes an alliance of research effort. This is likely to accelerate the discovery of important findings arising from both approaches, and to maximize the timely understanding of the longer-term consequences of childbirth practices.

The effect of medical and operative birth interventions on child health outcomes in the first 28 days and up to 5 years of age: A linked data population‐based cohort study

“…Establishing the gut microbiota may be important in protecting the child, and later the adult, against atopic and immunological diseases 10, 34. Disturbances in this process could be linked to developing infectious, inflammatory, and allergic diseases later in life 10, 34.…”

“…4,6,30,31 The EPIIC hypothesis postulated by some of the authors in this paper, proposes that nonphysiological interventions during the intrapartum period, and specifically the use of synthetic oxytocin, epidural analgesia, and cesarean delivery, may interrupt the normal stress of being born. 10,11 This could have an epigenetic effect on specific genes, such as those that program immune responses, including weight regulation and metabolism. In support of an epigenetic hypothesis in this area, an association between mode of birth and DNA methylation has previously been reported.…”

“…8,9 Establishing the gut microbiota may be important in protecting the child, and later the adult, against atopic and immunological diseases. 10,34 Disturbances in this process could be linked to developing infectious, inflammatory, and allergic diseases later in life. 10,34 However, some studies associate the mode of birth with differences in the child's microbiota, other conflicting results showed that there was no effect of cesarean delivery on the early microbiota beyond the immediate neonatal period.…”

“…This may potentially affect the neonatal immune response 8, 9. The EPIgenetic Impact of Childbirth (EPIIC) hypothesis raises concern over the effects of stress (too high and too low) caused by medical and operative birth interventions to the epigenetic regulation of gene expression in the immune system 10, 11…”

“…8,9 The EPIgenetic Impact of Childbirth (EPIIC) hypothesis raises concern over the effects of stress (too high and too low) caused by medical and operative birth interventions to the epigenetic regulation of gene expression in the immune system. 10,11 Studies have demonstrated that children born vaginally at term have different short-and longer-term physical health outcomes than those born by cesarean, particularly when there has been no exposure. 4,6,7 Epidemiological studies that analyzed population-based registry data, reported conflicting associations between operative birth interventions, and the increased risk of several immune-related diseases, including asthma, type 1 diabetes, obesity, and inflammatory bowel disease.…”