Biol. Rev. (2012), 87, pp. 229 – 243. 229 doi: 10.1111/j.1469-185X.2011.00195.x The health implications of birth by Caesarean section Matthew J. Hyde 1,* , Alison Mostyn 2 , Neena Modi 1 and Paul R. Kemp 3 1 Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster Campus, 369 Fulham Road, London, SW10 9HN, UK 2 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, UK 3 Section of Molecular Medicine, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK ABSTRACT Since the first mention of fetal programming of adult health and disease, a plethora of programming events in early life has been suggested. These have included intrauterine and postnatal events, but limited attention has been given to the potential contribution of the birth process to normal physiology and long-term health. Over the last 30 years a growing number of studies have demonstrated that babies born at term by vaginal delivery (VD) have significantly different physiology at birth to those born by Caesarean section (CS), particularly when there has been no exposure to labour, i.e. pre-labour CS (PLCS). This literature is reviewed here and the processes involved in VD that might programme post-natal development are discussed. Some of the effects of CS are short term, but longer term problems are also apparent. We suggest that VD initiates important physiological trajectories and the absence of this stimulus in CS has implications for adult health. There are a number of factors that might plausibly contribute to this programming, one of which is the hormonal surge or ‘‘stress response’’ of VD. Given the increasing incidence of elective PLCS, an understanding of the effects of VD on normal development is crucial. Key words: early life programming, vaginal delivery, Caesarean section, stress response, catecholamines, birth, labour, neonate, microflora, allergy. CONTENTS I. Introduction ................................................................................................ 230 II. Adaptations to postnatal life ................................................................................ 230 III. Short-term physiological changes in response to Caesarean section ........................................ 230 (1) Impaired lung function ................................................................................ 231 (2) Reduced thermogenic response ........................................................................ 231 (3) Altered metabolism .................................................................................... 231 (4) Altered feeding ......................................................................................... 231 (5) Altered immune phenotype ............................................................................ 232 (6) Altered blood pressure ................................................................................. 232 IV. Longer term effects of delivery by Caesarean section ....................................................... 232 (1) Immune-related conditions ............................................................................ 232 (2) Body mass .............................................................................................. 233 (3) Hepatic consequences .................................................................................. 233 (4) Neurological and stress-related problems .............................................................. 234 V. How might PLCS account for these physiological differences? ............................................. 234 (1) Hormonal responses at delivery ........................................................................ 234 (a) Catecholamines ..................................................................................... 234 (b) Cortisol ............................................................................................. 234 (c) Profile of other hormones ........................................................................... 234 (2) Colonisation of the intestinal tract ..................................................................... 235 * Address for correspondence (Tel: 02033 158241; E-mail: matthew.hyde02@imperial.ac.uk). Biological Reviews 87 (2012) 229 – 243  2011 The Authors. Biological Reviews  2011 Cambridge Philosophical Society