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Review Article METHOD OF DELIVERY, THE MICROBIOME AND NEURODEVELOPMENT Gregory V Lamb André van Niekerk Robin J Green Department of Paediatrics and Child Health, University of Pretoria Email | Greg.Lamb@up.ac.za ABSTRACT Caesarean sections, and especially elective Caesarean sections, are on the increase worldwide. The grey-matter volume of the foetal brain undergoes a linear increase of 1,4% per week from 29 weeks until 40 weeks of gestation. This is followed by an accelerated period of brain growth, during which 50% of the increase in cortical volume occurs, between 34 and 40 weeks of gestation. Between 37 and 40 weeks of gestation, cortical grey matter increases by 50% and myelinated white matter increases three-fold. According to the World Health Organisation (WHO), a baby is born prematurely if it is delivered before 37 completed weeks’ gestational age (GA), or before 259 days after the last normal menstrual period. As a result, the American College of Gynecologists and Obstetricians (ACOG) has adopted a new maturity classification that refers to babies born from 37 to 39 weeks as ‘early term’. Early-term neonates are at increased risk of morbidity. Prematurity is associated with impaired cortical development, and ex-premature infants never achieve the same degree of cortical folding as that seen in babies born at term. Prematurity is also a major risk factor for cerebral palsy, which occurs in 35% of cases. The increased risk is directly proportional to decreasing GA. The global prevalence of cerebral palsy is 2/1 000 births. Between 32 and 36 weeks of gestation, the risk increases to 6.75/1 000 births. Importantly for the timing of elective Caesarean section, there is still an increased risk of 1.35/1 000 births even after 36 weeks of gestation. Babies who are born in the early term period (between 37 and 39 weeks GA) will later constitute 5,5% of children with special educational needs (SEN). Even those babies born at 39 weeks GA carry an elevated risk and constitute 1,7% of total SEN cases. Normal vaginal delivery is associated with neonatal acquisition of a maternally derived microbiome that has a rich diversity. Through bacterial peptides, the microbiome stimulates immune, endocrine and neuronal cells to release cytokines and neurotransmitters, which access the central nervous system via the blood or the vagal nerve. In this way, enteric bacteria can influence mood and behaviour, sleep–wake cycles and feeding patterns. During Caesarean section, however, the foetus is colonised instead by bacteria from the mother’s skin. The microbiome that results from this has far less richness and diversity. This in turn is associated with significant risk for chronic inflammatory disorders in later life. New to our understanding of chronic inflammatory disorders that result from dysbiosis is a range of neuro-developmental problems in childhood and adults. INTRODUCTION now represent 10% of births worldwide.3 A lthough the worldwide incidence of Caesarean section is 25,7%,1 the incidence of Caesarean section in China – which, along with South Africa, is considered a Elective Caesarean sections, and the reduced gestation with which they come, may, however, come at a neuro- developing country – rose dramatically from 22% in 1994 developmental cost. The last four weeks of gestation are to 56% in 2006.2 Elective Caesarean sections are following essential for brain programming.4 Foetal and neonatal a similar trend, with the WHO confirming that such sections brain development take place along a continuum, and 130 Current Allergy & Clinical Immunology | September 2017 | Vol 30, No 3 REVIEW ARTICLE Figure 1: The end of the third trimester is a critical period for the formation of synapses and apoptosis of redundant neurons. complex organisational changes occur during both intra- Figure 2: Synaptogenesis (the connectivity between neurons) occurs at the rate of 40 000 synapses per minute during foetal development so that by and extrauterine development (Figure 1). 5 the end of gestation, the foetal brain should consist of approximately 100 million neurons.7,8 DEVELOPMENT OF THE BRAIN The grey matter volume of the foetal brain undergoes a There has been a dramatic rise in preterm births globally.10 linear increase of 1.4% per week from 29 weeks until 40 The associated m

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