|Year : 2020 | Volume
| Issue : 1 | Page : 3-7
Cesarean section delivery and the autism spectrum disorder: Risk and consequences in Bangladesh
Rashed Noor, Syeda Muntaka Maniha, Masuma Afrin Taniya
Department of Microbiology, School of Life Sciences, Independent University Bangladesh, Dhaka, Bangladesh
|Date of Submission||02-Oct-2019|
|Date of Acceptance||18-Nov-2019|
|Date of Web Publication||17-Mar-2020|
Dr. Rashed Noor
School of Life Sciences, Independent University Bangladesh, Plot 16, Block B, Aftab Uddin Ahmed Road, Bashundhara, Dhaka 1229
Source of Support: None, Conflict of Interest: None
Long-term health problems such as an elevated rate of developing obesity and asthma; and most importantly the neurodevelopmental problem of the children born by cesarean section delivery is very likely which in turn may lead to autism or attention deficit disorder. The survival and proliferation of the infant gut microbiota in relation to the mode of delivery is noteworthy because of its ultimate impact on the psychological and neurological behavior of the children. Studies so far conducted on the detrimental long-term outcomes linked with the cesarean delivery, a great deal of evidences have been found about the gut bacterial composition acquired by the infants. The early life dysbacteriosis or the imbalance of the resident microflora may hamper the protective immunity accompanied with inflammatory diseases which is also coupled with the neurological malfunction leading to autism spectra. Therefore, the intentional delivery through the C-section needs to be reduced which is unfortunately a very common case in the underdeveloped and developing countries with lack of such technical information among the huge population. Current review focused on the impact of alteration of the infant gut microorganisms (caused by the cesarean delivery) leading to the autism spectrum disorder; and concentrated on the dissemination of such knowledge in the mass community from the public health perspective.
Keywords: Autism spectrum disorder, cesarean section delivery, gut microorganisms, public health
|How to cite this article:|
Noor R, Maniha SM, Taniya MA. Cesarean section delivery and the autism spectrum disorder: Risk and consequences in Bangladesh. Biomed Biotechnol Res J 2020;4:3-7
|How to cite this URL:|
Noor R, Maniha SM, Taniya MA. Cesarean section delivery and the autism spectrum disorder: Risk and consequences in Bangladesh. Biomed Biotechnol Res J [serial online] 2020 [cited 2020 Jun 4];4:3-7. Available from: http://www.bmbtrj.org/text.asp?2020/4/1/3/280859
| Introduction|| |
Compared with the vaginal delivery, there is a certain link between the cesarean section (CS) and the autism spectrum disorder (ASD) which has been noticed to be rigorously accelerated principally triggered by certain environmental and genetic factors over the last four decades.,,,, The largest population-based study (from Norway, Sweden, Denmark, Finland and Western Australia) by Yip et al. (2017) comprehensively showed that the births delivered by CS had a higher risk of ASD over the vaginal delivery (36–42 weeks of gestation). While the vaginal delivery is likely to initiate positive changes in the epigenetic expression as well as to enhance the immune system, the CS delivery system may largely affect the newborn with the exposure to the skin microbiota).,,, The CS delivery is known to change the developing gut microbiota too. Such a condition is alarming since the gut microbiota may communicate with the central nervous system (CNS) probably through the neural, endocrine and immune pathways and thereby influencing the brain function and behavior, anxiety, mood, cognition, and pain.,
Interestingly, a difference was noticed among the microbiota in breast milk of the women who delivered vaginally and those who underwent the CS delivery.,, A study pointed that the common gut bacterium Lactobacillus johnsonii ound to relatively dominant in the vaginal flora of pregnant women compared to the nonpregnant individuals., Once ingested by the neonate during vaginal delivery, the gut microbiota may play a significant role in shaping the infant gut microbial community. Therefore, the CS delivery appears to be both clinically and psychologically critical for the newborn.
In many developing countries like Bangladesh, a very unfortunate event has been noticed especially within the last couple of years that the physicians somehow encourage their patients to go for a C-section delivery (more 50% CS delivery) rather than the vaginal delivery. From the microbiological point of view, infants coming out through the vagina are likely to be exposed to the beneficial gut microbiome which, in other words, confer them the protective immunity. Since the gut and brain are connected through the vagus nerves, the metabolites produced by the gut microbiome may send signals through the vagus nerves. Thus the critical period of brain development apparently resembles to a sort of mimicry of gut microbiome development.
As the infants delivered through the CS system are not exposed to vaginal microbiome, their gut microbiome composition is eventually affected; and such a dysbiosis in the gut microbiome composition of the infant goes a long way to affect the healthy brain development. As a result, these infants become susceptible to the neurological disorders afterwards like the ASDs. Current review attempted to communicate the knowledge among the general people about the harmful effects of the CS delivery system in order to bring up healthy children which indeed are a major part of maintaining a sustainable state of sound public health.
| Benefits of Gut Microorganisms|| |
The human gut serves as the suitable habitat for an array of beneficiary microorganisms which are known to impart the health sustainability along with the elevation of host defenses against the pathogenic attack possibly by supplying the necessary metabolites as well as by activating the host's protective immune system.,, The most dominating and health advantageous gut microflora include Firmicutes (Clostridium, Enterococcus, Lactobacillus, and Ruminococcus), Bacteroidetes (Bacteroides and Prevotella) and to a minor boundary, Proteobacteria and Actinobacteria., Several primary and secondary metabolites (bile acids, butyrate, antimicrobial peptides; i.e., AMPs,) secreted by the gut bacterial metabolism may kill the pathogenic bacteria., Activation of macrophages, neutrophils, inflammatory monocytes, interleukin (IL)-22, the innate lymphoid cells followed by the production of immunoglobulins IgA and IgM are also triggered by the gut microbial activities., Therefore, alteration of the composition of gut microbiome may lead to the serious health damages ranging from the cardiovascular diseases to even the onset of ASD.,,,,
| Alteration of Gut Microorganisms by Cesarean Section Delivery and the Onset of Autism Spectrum Disorder|| |
Usually the gut microbiome in the newborn is fewer compared to an adult. Besides the gut-brain axis and the antibiotic exposure or the feeding patterns; the most influencing factor for the gut microbiome development (especially with the four main phyla: Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria) is the mode of delivery. To date, there are lots of evidences on the impact of the delivery mode on the gut microbiota consortium in the infants.,, The systematic analyses by Rutayisire et al. (2016) and Yang et al. in 2016 showed the CS delivery mode to be associated with a low proliferation of Actinobacteria (Bifidobacterium, Atopobium, Corynebacterium, Propionibacterium) and Bacteroidetes (Bacteroide fragilis, B. vulgates, Prevotella spp.) and an abnormal elevation of Enterococcus spp., Clostridium perfringens, C. defficile, Ruminococcus spp., Streptococcus spp., Staphylococcus epidermidis, Escherichia More Details coli, Klebsiella spp., Enterobacter spp. from birth to 3 months of the infants' gut [Figure 1]., As stated earlier, this is worth to note that the healthy gut microbiota promotes the protective immunity [transferred by the normal or vaginal delivery, as shown in [Figure 2] while the abnormal gut flora may trigger the dreadful gastrointestinal infections during the infancy. A very recent meta-analysis by Zhang et al. (2019) used 61 previously published studies, and the data included more than 20 million deliveries, of which it was noticed that the birth by CS was associated with a 33% higher risk of autism and 17% higher risk of attention deficit disorder.,
|Figure 1: Cesarean section delivery and the onset of autism spectrum disorder. The cesarean section delivery diminishes or decreases the proliferation of normal gut microbiota including Actinobacteria and Bacteroidetes accompanied with an abnormal elevation of the mother's skin microflora (like Staphylococcus epidermidis), and the other bacteria harmful (including Clostridium perfringens, Clostridium defficile, Streptococcus spp., and Enterobacteriaceae) for the infant. Such abnormal gut flora in the newborn may induce the pathogenic infections while the lower level of the normal gut microbiota may evoke the production of the inflammatory cytokines which are likely to affect the central nervous system and hence present abnormal neurological activities including the onset of the autism spectrum disorder|
Click here to view
|Figure 2: Beneficial effect of vaginal delivery on the infant. The vaginal delivery permits the normal gut microbiota (Lactobacillus, Ruminococcus, Bacteroides, Actinobacteria, Prevotella, etc.) to be transferred to the newborn which in turn promote the health sustainability through the elevation of necessary host defenses against the pathogenic attack and by providing the essential metabolites (including bile acids, butyrate, antimicrobial peptides, etc.). Activation of innate immunity as well as the production of necessary immunoglobulins is also mediated by such transfer of gut microbiota from mother to the newborn|
Click here to view
It is to be pondered that within 90 days of birth, the normal gut phyla diversity of Actinobacteria and Bacteroidetes (Bifidobacterium and Bacteroides) may be decreased in the infants delivered by the CS method than those delivered vaginally. Moreover, in the infants, gut colonization with Lactobacillus (through a vaginal delivery) lowers the levels of interferon-gamma, IL-10, and IL-4; whereas, colonization with the skin microorganism Staphylococcus aureus (resultant of a CS delivery) is likely to heighten the inflammatory cytokine levels which in turn, may affect the CNS, mood, stress response, and behavioral activities including fatigue and depression accompanied with insomnia and the loss of appetite.,
| Frequency, Causes and Effects of Cesarean Section Delivery Cases in Bangladesh|| |
In Bangladesh the child delivery mode using the CS (C-section or CS) is unnecessarily thought to be a means of saving lives of women and their newborns as well as an easy way from getting rid of birth related complications. As reported by Begum et al. (2017), Bangladesh Demographic and Health Survey 2014 had showed that among 37% facility delivery, 60% was conducted in the for-profit private sector hospitals (NIPORT, Mitra and Associates, and ICF International; 2015). Moreover, it was noticed that the CS delivery rate had increased from 4% in 2004 to 23% in 2014 (Begum et al., 2017; NIPORT, Mitra and Associates, and ICF International; 2014).,, Such terrible situation happened principally due to the lack of knowledge about the adverse impacts on the infant health through the C-section delivery. Besides, most of the health professionals also lack the precise knowledge on the disruption of the protective immunity let alone the ASD directly or indirectly triggered by the alteration of gut microflora during the CS delivery. The third reason to be pondered is that both the technical and perceived quality of maternal and neonatal health care is very poor in both public and private facilities in Bangladesh., Most unfortunately, the basic emergency obstetric care services in Bangladesh are very scarce; and the hospitals are devoid of the essential equipments together with a poor medical practice. The other reasons for the increased rate of CS delivery in Bangladesh may be to avoid the prolonged labor in case of a normal/vaginal delivery as well as due to the advance maternal age.,
Surprisingly, there is not much study or research linking the CS delivery system to child autism in Bangladesh. Research on gut bacteria influencing the ASD is also very inadequate. Finally, how the CS delivery mode influences the onset of ASD is still unclear or in other words, absolutely unknown to most of the health professionals. Such a situation would clearly elevate the current rate CS delivery day by day. Hence, the microbial knowledge on the alteration of gut microbiota through the CS delivery system should be disseminated not only among the health professionals working both in the private and public sectors, but also it should be propagated among the general people. Acquiring knowledge on the detrimental outcome of CS delivery (especially about the ASD) may discourage the mass people to go for CS delivery. Further work by the medical doctors and other health professionals on the link between the gut microbiota and neurological output would draw a conclusive effort to reduce the unnecessary practice CS delivery behavior.
| Conclusion|| |
Before birth, microorganisms residing within the mother's gut perform essential metabolic and digestives functions accompanied with the development and activation of the protective immune system; and most interestingly, the production of neurotransmitters which are very likely to influence the behavior and the cognitive function of the infant. From a number of studies so far conducted on the microbiology of the CS-delivery and the vaginal delivery systems, it is clearly proven and understood that during a vaginal birth, the infants acquire beneficial microbiome from its mother which is not possible in case of a caesarian case. As a result, the infant after birth may suffer from various clinical complications to the point of psychological and behavioral problems due to neurological problems. People especially of the third world countries like Bangladesh should be aware of such knowledge and outcomes of a C-section delivery which is very much frequent here.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Yip BH, Leonard H, Stock S, Stoltenberg C, Francis RW, Gissler M, et al
. Caesarean section and risk of autism across gestational age: A multi-national cohort study of 5 million births. Int J Epidemiol 2017;46:429-39.
Curran EA, O'Neill SM, Cryan JF, Kenny LC, Dinan TG, Khashan AS, et al
. Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. J Child Psychol Psychiatry 2015;56:500-8.
Almgren M, Schlinzig T, Gomez-Cabrero D, Gunnar A, Sundin M, Johansson S, et al
. Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: Implications for future health? Am J Obstet Gynecol 2014;211:502.e1-8.
Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA 2014;311:1770-7.
Leonard H, Dixon G, Whitehouse AJO, Bourke J, Aiberti K, Nassar N, et al
. Unpacking the complex nature of the autism epidemic. Res Autism Spectr Disord 2010;4:548-54.
Song SJ, Dominguez-Bello MG, Knight R. How delivery mode and feeding can shape the bacterial community in the infant gut. CMAJ 2013;185:373-4.
Cryan JF, Dinan TG. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 2012;13:701-12.
Holzer P. Neuropeptides, Microbiota, and Behavior. Int Rev Neurobiol 2016;131:67-89.
Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr 2012;96:544-51.
Aagaard K, Riehle K, Ma J, Segata N, Mistretta TA, Coarfa C, et al
. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS One 2012;7:e36466.
Chen H, Tan D. Cesarean section or natural childbirth? Cesarean birth may damage your health. Front Psychol 2019;10:351.
Yang I, Corwin EJ, Brennan PA, Jordan S, Murphy JR, Dunlop A. The infant microbiome: Implications for infant health and neurocognitive development. Nurs Res 2016;65:76-88.
Lach G, Schellekens H, Dinan TG, Cryan JF. Anxiety, depression, and the microbiome: A role for gut peptides. Neurotherapeutics 2018;15:36-59.
Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry 2016;21:738-48.
Hillman ET, Lu H, Yao T, Nakatsu CH. Microbial ecology along the gastrointestinal tract. Microbes Environ 2017;32:300-13.
Pickard JM, Zeng MY, Caruso R, Núñez G. Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev 2017;279:70-89.
Rutayisire E, Huang K, Liu Y, Tao F. The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants' life: A systematic review. BMC Gastroenterol 2016;16:86.
Power SE, O'Toole PW, Stanton C, Ross RP, Fitzgerald GF. Intestinal microbiota, diet and health. Br J Nutr 2014;111:387-402.
Liu H, Chen X, Hu X, Niu H, Tian R, Wang H, et al
. Alterations in the gut microbiome and metabolism with coronary artery disease severity. Microbiome 2019;7:68.
Gaufin T, Tobin NH, Aldrovandi GM. The importance of the microbiome in pediatrics and pediatric infectious diseases. Curr Opin Pediatr 2018;30:117-24.
Zhang T, Sidorchuk A, Sevilla-Cermeño L, Vilaplana-Pérez A, Chang Z, Larsson H, et al
. Association of cesarean delivery with risk of neurodevelopmental and psychiatric disorders in the offspring: A systematic review and meta-analysis. JAMA Netw Open 2019;2:e1910236.
Johansson MA, Saghafian-Hedengren S, Haileselassie Y, Roos S, Troye-Blomberg M, Nilsson C, et al
. Early-life gut bacteria associate with IL-4-, IL-10- and IFN-γ production at two years of age. PLoS One 2012;7:e49315.
Begum T, Rahman A, Nababan H, Hoque DME, Khan AF, Ali T, et al
. Indications and determinants of caesarean section delivery: Evidence from a population-based study in Matlab, Bangladesh. PLoS One 2017;12:e0188074.
National Institute of Population Research and Training (NIPORT) MaA, and ICF International. Bangladesh Demographic and Health Survey 2014: Key Indicators. Dhaka, Bangladesh, and Rockville, Maryland, USA: National Institute of Population Research and Training, Mitra and Associates, and ICF International; 2015.
National Institute of Population Research and Training (NIPORT) MaA, and ICF International. Bangladesh Demographic and Health Survey 2014: Key Indicators. Dhaka, Bangladesh, and Rockville, Maryland, USA: National Institute of Population Research and Training, Mitra and Associates, and ICF International; 2014.
Cockcroft A, Milne D, Oelofsen M, Karim E, Andersson N. Health services reform in Bangladesh: Hearing the views of health workers and their professional bodies. BMC Health Serv Res 2011;11 Suppl 2:S8.
Anwar I, Kalim N, Koblinsky M. Quality of obstetric care in public-sector facilities and constraints to implementing emergency obstetric care services: Evidence from high- and low-performing districts of Bangladesh. J Health Popul Nutr 2009;27:139-55.
Aminu M, Utz B, Halim A, van den Broek N. Reasons for performing a caesarean section in public hospitals in rural Bangladesh. BMC Pregnancy Childbirth 2014;14:130.
[Figure 1], [Figure 2]