Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-10T05:39:57.189Z Has data issue: false hasContentIssue false
  • English
  • Français

Bacterial Baptism: Scientific, Medical, and Regulatory Issues Raised by Vaginal Seeding of C-Section-Born Babies

Published online by Cambridge University Press:  01 January 2021

Noel T. Mueller ,
Suchitra K. Hourigan ,
Diane E. Hoffmann ,
Lauren Levy ,
Erik C. von Rosenvinge ,
Betty Chou  and
Maria-Gloria Dominguez-Bello
Get access Rights & Permissions [Opens in a new window]

Abstract

Several lines of evidence suggest that children born via Cesarean section (C-section) are at greater risk for adverse health outcomes including allergies, asthma and obesity. Vaginal seeding is a medical procedure in which infants born by C-section are swabbed immediately after birth with vaginal secretions from the mother. This procedure has been proposed as a way to transfer the mother's vaginal microbiome to the child, thereby restoring the natural exposure that occurs during vaginal birth that is interrupted in the case of babies born via C-section. Preliminary evidence indicates partial restoration of microbes. However, there is insufficient evidence to determine the health benefits of the procedure. Several studies, including trial, are currently underway. At the same time, in the clinic setting, doctors are increasingly being asked to by expectant mothers to have their babies seeded. This article reports on the current research on this procedure and the issues it raises for regulators, researchers, physicians, and patients.

Type
Symposium 1 Articles
Information
Journal of Law, Medicine & Ethics , Volume 47 , Issue 4: Symposium 1 - The Promise and Challenges of Microbiome-based Therapies. Symposium 2 - Regulation on International Direct-to-Participant Genomic Research , Winter 2019 , pp. 568 - 578
Copyright
Copyright © American Society of Law, Medicine and Ethics 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Boerma, T., Ronsmans, C., and Melesse, D.Y. et al., “Global Epidemiology of Use of and Disparities in Caesarean Sections,” Lancet 392 (2018): 1341–1348.CrossRefGoogle Scholar
National Center for Health Statistics, FastStats: Births — Method of Delivery, available at <https://www.cdc.gov/nchs/fastats/delivery.htm> (last visited October 1, 2019).+(last+visited+October+1,+2019).>Google Scholar
World Health Organization, Statement on Cesarean Section Rates (April 2015), available at <https://www.who.int/reproductivehealth/publications/maternal_perinatal_health/cs-statement/en> (last visited October 1, 2019).+(last+visited+October+1,+2019).>Google Scholar
Visser, G.H.A., Ayres de Campos, D., and Barnea, E.R. et al., “FIGO Position Paper: How to Stop the Caesarean Section Epidemic,” Lancet 392 (2018): 1286–1287.CrossRefGoogle Scholar
Sandall, J., Tribe, R.M., and Avery, L. et al., “Short-Term and Long-Term Effects of Caesarean Section on the Health of Women and Children,” Lancet 392 (2018):1349–1357.Google Scholar
Mueller, N.T., Zhang, M., Hoyo, C., Østbye, T., and Benjamin-Neelon, S.E., “Does Cesarean Delivery Impact Infant Weight Gain and Adiposity Over the First Year of Life?” International Journal of Obesity 43, no. 8 (2018): 1549–1555.CrossRefGoogle Scholar
Huh, S.Y., Rifas-Shiman, S.L., and Zer, C.A. et al., “Delivery by Caesarean Section and the Risk of Obesity in Preschool Age Children: A Prospective Cohort Study,” Archives of Disease in Childhood 97, no. 7 (2012): 610–616.CrossRefGoogle Scholar
Darmasseelane, K., Hyde, M.J., Santhakumaran, S., Gale, C., and Modi, N., “Mode of Delivery and Offspring Body Mass Index, Overweight and Obesity in Adult Life: A Systematic Review and Meta-Analysis,” PLoS One 9, no. 2 (2014): e87896.CrossRefGoogle Scholar
Li, H.T., Zhou, Y.B., and Liu, J.M., “The Impact of Cesarean Section on Offspring Overweight and Obesity: A Systematic Review and Meta-Analysis,” International Journal of Obesity 37, no. 7 (2013): 893–899; Darmasseelane et al., supra note 8; Kuhle, S., Tong, O.S., and Woolcott, C.G., “Association Between Caesarean Section and Childhood Obesity: A Systematic Review and Meta-Analysis,” Obesity Review 16, no. 4 (2015): 295–303.CrossRefGoogle Scholar
Renz-Polster, H., David, M.R., and Buist, A.S. et al., “Caesarean Section Delivery and the Risk of Allergic Disorders in Childhood,” Clinical and Experimental Allergy 35, no. 11 (2005): 1466–1472.CrossRefGoogle Scholar
Magnus, M.C., Håberg, S.E., and Stigum, H. et al., “Delivery by Cesarean Section and Early Childhood Respiratory Symptoms and Disorders: The Norwegian Mother and Child Cohort Study,” American Journal of Epidemiology 174, no. 11 (2011): 1275–1285; Almqvist, C., Cnattingius, S., Lichtenstein, P., and Lundholm, C., “The Impact of Birth Mode of Delivery on Childhood Asthma and Allergic Diseases–A Sibling Study,” Clinical and Experimental Allergy 42, no. 9 (2012): 1369–1376; Kero, J., Gissler, M., and Grönlund, M.M. et al., “Mode of Delivery and Asthma–Is there a Connection?” Pediatric Research 52, no. 1 (2002): 6–11; Salam, M.T., Margolis, H.G., and McConnell, R. et al., “Mode of Delivery is Associated with Asthma and Allergy Occurrences in Children,” Annals of Epidemiology, no. 5 (2006): 341–346; Huang, L., Chen, Q., and Zhao, Y. et al., “Is Elective Cesarean Section Associated with a Higher Risk of Asthma? A Meta-Analysis,” Journal of Asthma 52, no. 1 (2015): 16–25; Park, Y.H., Kim, K.W., and Choi, B.S. et al., “Relationship Between Mode of Delivery in Childbirth and Prevalence of Allergic Diseases in Korean Children,” Allergy, Asthma & Immunology Research 2, no.1 (2010): 28–33; Juhn, Y.J., Weaver, A., Katusic, S., and Yunginger, J., “Mode of Delivery at Birth and Development of Asthma: A Population-Based Cohort Study,” Journal of Allergy and Clinical Immunology 116, no. 3 (2005): 510–516; Maitra, A., Sherriff, A., and Strachan, D. et al., “Mode of Delivery is Not Associated with Asthma or Atopy in Childhood,” Clinical & Experimental Allergy 34, no. 9 (2004): 1349–1355.CrossRefGoogle Scholar
Sevelsted, A., Stokholm, J., Bønnelykke, K., and Bisgaard, H., “Cesarean Section and Chronic Immune Disorders,” Pediatrics 135, no. 1 (2015): e92–e98.Google Scholar
Mitselou, N., Hallberg, J., and Stephansson, O. et al., “Cesarean Delivery, Preterm Birth, and Risk of Food Allergy: Nationwide Swedish Cohort Study of More than 1 Million Children,” Journal of Allergy and Clinical Immunology 142, no. 5 (2018): 1510–14.e2.CrossRefGoogle Scholar
Mueller, E., Bakacs, E., Combellick, J., Grigoryan, Z., and Dominguez-Bello, M.G., “The Infant Microbiome Development: Mom Matters,” Trends in Molecular Medicine 21, no. 2 (2015): 109–117.CrossRefGoogle Scholar
Dominguez-Bello, M.G., Costello, E.K., and Contreras, M. et al., “Delivery Mode Shapes the Acquisition and Structure of the Initial Microbiota across Multiple Body Habitats in Newborns,” Proceedings of the National Academies of Science of the United States of America 107, no. 26 (2010): 11971–11975.CrossRefGoogle Scholar
Iacobucci, G., “Sixty Seconds on … Vaginal Seeding,” BMJ 352 (2016): i1095.Google Scholar
Dominguez-Bello, M.G., De Jesus-Laboy, K.M., and Shen, N. et al., “Partial Restoration of the Microbiota of Cesarean-Born Infants via Vaginal Microbial Transfer,” Nature Medicine 22, no. 3 (2016): 250–253.Google Scholar
Id.Google Scholar
Huynh, J., Palasanthiran, P., and McMullan, B., “Potential Transmission of Herpes Simplex Virus via Vaginal Seeding,” The Pediatric Infectious Disease Journal 37, no. 11 (2018): e278.CrossRefGoogle Scholar
Cunnington, A.J., Sim, K., Deierl, A., Kroll, J.S., Brannigan, E., and Darby, J., “‘Vaginal Seeding’ of Infants Born by Caesarean Section,” BMJ 352 (2016): i227.CrossRefGoogle Scholar
Committee on Obstetric Practice, supra note 14.Google Scholar
Haahr, T., Glavind, J., and Axelsson, P. et al., “Vaginal Seeding or Vaginal Microbial Transfer from the Mother to the Caesarean-Born Neonate: A Commentary Regarding Clinical Management,” BJOG 125, no. 5 (Apr. 2018): 533–536, doi: 10.1111/1471-0528.14792.CrossRefGoogle Scholar
Yassour, M., Vatanen, T., and Siljander, H. et al., “Natural History of the Infant Gut Microbiome and Impact of Antibiotic Treatment on Bacterial Strain Diversity and Stability,” Science Translational Medicine 8, no. 343 (2016): 343ra381; Bokulich, N.A., Chung, J., and Battaglia, T. et al., “Antibiotics, Birth Mode, and Diet Shape Microbiome Maturation During Early Life,” Science Translational Medicine, no. 343 (2016): 343ra382; Yatsunenko, T., Rey, F.E., and Manary, M.J. et al., “Human Gut Microbiome Viewed across Age and Geography,” Nature 486, no. 7402 (2012): 222–227.Google Scholar
Dominguez-Bello et al., supra note 15.Google Scholar
Mueller, supra note 14; Haahr et al., supra note 22.Google Scholar
Mueller, supra note 14.Google Scholar
Bäckhed, F., Roswall, J., and Peng, Y. et al., “Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life,” Cell Host and Microbe 17, no. 5 (2015): 690–703; Goedert, J.J., Hua, X., Yu, G., and Shi, J., “Diversity and Composition of the Adult Fecal Microbiome Associated with History of Cesarean Birth or Appendectomy: Analysis of the American Gut Project,” EBioMedicine 1, no. 2-3 (2014): 167–172; Chernikova, D.A., Koestler, D.C., and Hoen, A.G. et al., “Fetal Exposures and Perinatal Influences on the Stool Microbiota of Premature Infants,” Journal of Maternal-Fetal and Neonatal Medicine 29, no. 1 (2016): 99–105; Kabeerdoss, J., Ferdous, S., and Balamurugan, R. et al., “Development of the Gut Microbiota in Southern Indian Infants from Birth to 6 Months: A Molecular Analysis,” Journal of Nutritional Science 2 (2013): e18; Dominguez-Bello et al., supra note 15; Sordillo, J.E., Zhou, Y., and McGeachie, M.J. et al., “Factors Influencing the Infant Gut Microbiome at Age 3-6 Months: Findings from the Ethnically Diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART),” Journal of Allergy and Clinical Immunology 139, no. 2 (2017): 482–91.e414; Levin, A.M., Sitarik, A.R., and Havstad, S.L. et al., “Joint Effects of Pregnancy, Sociocultural, and Environmental Factors on Early Life Gut Microbiome Structure and Diversity,” Scientific Reports 6 (2016): art. no. 31775; Martin, R., Makino, H., and Cetinyurek Yavuz, A. et al., “Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota,” PLoS One 11, no. 6 (2016): e0158498; Lee, E., Kim, B.J., and Kang, M.J. et al., “Dynamics of Gut Microbiota According to the Delivery Mode in Healthy Korean Infants,” Allergy Asthma and Immunology Research 8, no. 5 (2016): 471–477; Bosch, A., Levin, E., and van Houten, M.A. et al., “Development of Upper Respiratory Tract Microbiota in Infancy is Affected by Mode of Delivery,” EBioMedicine 9 (2016): 336–345; Bokulich, N.A., Chung, J., and Battaglia, T. et al., “Antibiotics, Birth Mode, and Diet Shape Microbiome Maturation During Early Life,” Science Translational Medicine 8, no. 343 (2016): 343ra382; Yassour, M., Vatanen, T., and Siljander, H. et al., “Natural History of the Infant Gut Microbiome and Impact of Antibiotic Treatment on Bacterial Strain Diversity and Stability,” Science Translational Medicine 8, no. 343 (2016): 343ra381; Zeber-Lubecka, N., Kulecka, M., and Ambrozkiewicz, F. et al., “Effect of Saccharomyces boulardii and Mode of Delivery on the Early Development of the Gut Microbial Community in Preterm Infants,” PLoS One 11, no. 2 (2016): e0150306; Madan, J.C., Hoen, A.G., and Lundgren, S.N. et al., “Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants,” JAMA Pediatrics 170, no. 3 (2016): 212–219; Chi, C., Xue, Y., and Lv, N. et al., “Longitudinal Gut Bacterial Colonization and Its Influencing Factors of Low Birth Weight Infants During the First 3 Months of Life,” Frontiers in Microbiology 10 (2019): art. no. 1105; Mueller, N.T., Shin, H., and Pizoni, A. et al., “Delivery Mode and the Transition of Pioneering Gut-Microbiota Structure, Composition and Predicted Metabolic Function,” Genes (Basel) 8, no. 12 (2017): E364; Fouhy, F., Watkins, C., and Hill, C.J. et al., “Perinatal Factors Affect the Gut Micro-biota up to Four Years after Birth,” Nature Communications 10, no. 1 (2019): art. no. 1517; Liu, Y., Qin, S., and Song, Y. et al., “The Perturbation of Infant Gut Microbiota Caused by Cesarean Delivery Is Partially Restored by Exclusive Breastfeeding,” Frontiers in Microbiology 10 (2019): art. no. 598; Wampach, L., Heintz-Buschart, A., and Fritz, J.V. et al., “Birth Mode Is Associated with Earliest Strain-Conferred Gut Microbiome Functions and Immunostimulatory Potential,” Nature Communications 9, no. 1 (2018): art. no. 5091; Li, H., Wang, J., and Wu, L. et al., “The Impacts of Delivery Mode on Infant's Oral Microflora,” Scientific Reports 8 (2018): art. no. 11938; Tun, H.M., Bridgman, S.L., and Chari, R. et al., “Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring,” JAMA Pediatrics 172, no. 4 (2018): 368–377; Shi, Y.C., Guo, H., and Chen, J. et al., “Initial Meconium Microbiome in Chinese Neonates Delivered Naturally or by Cesarean Section,” Scientific Reports 8, no. 1 (2018): art. no. 3255; Wampach, L., Heintz-Buschart, A., and Hogan, A. et al., “Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life,” Frontiers in Microbiology 8, no. 1 (2017): art. no. 738; Hill, C.J., Lynch, D.B., and Murphy, K. et al., “Evolution of Gut Microbiota Composition from Birth to 24 weeks in the INFANTMET Cohort,” Microbiome 5, no. 1 (2017): art. no. 4; Gregory, K.E., LaPlante, R.D., Shan, G., Kumar, D.V., and Gregas, M., “Mode of Birth Influences Preterm Infant Intestinal Colonization with Bacteroides over the Early Neonatal Period,” Advances in Neonatal Care 15, no. 6 (2015): 386–393.CrossRefGoogle Scholar
Chu, D.M., Ma, J., Prince, A.L., Antony, K.M., Seferovic, M.D., and Aagaard, K.M., “Maturation of the Infant Microbiome Community Structure and Function across Multiple Body Sites and in Relation to Mode of Delivery,” Nature Medicine 23, no. 3 (2017): 314–326.CrossRefGoogle Scholar
Id.Google Scholar
Fouhy, F., Watkins, C., and Hill, C.J. et al., “Perinatal Factors Affect the Gut Microbiota up to Four Years after Birth,” Nature Communications 10 (2019): art. no. 1517.Google Scholar
Cox, L.M., Yamanishi, S., and Sohn, J. et al., “Altering the Intestinal Microbiota During a Critical Developmental Window Has Lasting Metabolic Consequences,” Cell 158, no. 4 (2014): 705–721.CrossRefGoogle Scholar
ClinicalTrials.gov Identifier: NCT03809390.Google Scholar
ClinicalTrials.gov identifier: NCT03298334.Google Scholar
Standard of care testing includes gonorrhea, chlamydia, hepatitis B, HIV, and syphilis.Google Scholar
ClinicalTrials.gov identifier: NCT03567707.Google Scholar
Stein, R., “Doctors Test Bacterial Smear After Cesarean Sections to Bolster Babies' Microbiomes,” Morning Edition, National Public Radio, October 30, 2018, available at <https://www.npr.org/sections/health-shots/2018/10/30/658254175/doctors-test-bacterial-smear-after-cesarean-sections-to-bolster-babies-microbiom> (last visited October 1, 2019).Google Scholar
Committee on Obstetric Practice, supra note 14.Google Scholar
Wells, K., “The Miracle of Microbirth: What Every Mother Should Know,” Wellness Mama (Feb. 27, 2017, updated July 30, 2019), available at <https://wellnessmama.com/pod-cast/microbirth/> (last visited October 1, 2019); Microbirth, directed by Harman, T. and Wakeford, A. (Alto Films, 2014).Google Scholar
Smith, M.D., “Vaginal Seeding: Fact or Fiction?” Kamm McK-enzie OBGYN Blog, available at <https://www.kmobgyn.com/blog/entryid/136/vaginal-seeding-raleigh> (last visited October 1, 2019); Ruhl, C., “Vaginal Seeding: Sound Science or Just a Trend?” Healthy Mom and Baby, available at <https://www.health4mom.org/vaginal-seeding-sound-science-just-trend/> (last visited October 1, 2019); Hayes, C., “What We Don't Know about Vaginal Seeding,” MedPage Today's KevinMD, June 16, 2016, available at <https://www.kevinmd.com/blog/2016/06/dont-know-vaginal-seeding.html> (last visited December 9, 2019); Mitra, A., “Vaginal Seeding After Caesarean Section,” Gynae Geek, August 24, 2017, available at <https://www.gynaegeek.com/the-blog/2017/8/24/vaginal-seeding-after-caesarean-section> (last visited October 1, 2019).Google Scholar
Austin, J., “XX Factor: Forget What You've Read. Swabbing Your Baby with Vaginal Juices is Pointless and Weird,” Slate, February 10, 2016, available at <https://slate.com/human-interest/2016/02/dousing-your-newborn-in-vaginal-juices-is-pointless-and-weird.html> (last visited October 1, 2019).Google Scholar
Tuteur, A., “Warning: Vaginal Seeding Doesn't Work and May Be Harmful,” The Skeptical OB, Feb. 24, 2016, available at <http://www.skepticalob.com/2016/02/warning-vaginal-seeding-doesnt-work-and-may-be-harmful.html> (last visited October 1, 2019).Google Scholar
Committee on Obstetric Practice, supra note 14.Google Scholar
Biological products are a subcategory of drugs, defined by FDA as “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product … applicable to the prevention, treatment, or cure of a disease or condition of human beings.” 42 U.S.C. § 262(i).Google Scholar
21 U.S.C. § 321(g)(1).Google Scholar
U.S. Food & Drug Administration, Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies, Guidance for Industry, July 2013, available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-regarding-investigational-new-drug-requirements-use-fecal-microbiota> (last visited October 1, 2019).+(last+visited+October+1,+2019).>Google Scholar
45 C.F.R. § 46.111(a)(6); 21 C.F.R. § 56.111(a)(6).Google Scholar
U.S. Food & Drug Administration, Pre-IND Meeting Denial Letter, Jan. 29, 2018. Provided by authors; U.S. Food & Drug Administration, Guidance for Clinical Investigators, Sponsors and IRBs, Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted Without an IND, Sept. 2013, available at <https://www.fda.gov/downloads/drugs/guidances/ucm229175.pdf> (last visited October 1, 2019).+(last+visited+October+1,+2019).>Google Scholar
21 U.S.C. § 379(a).Google Scholar
836 F.3d 1199 (9th Cir. 2016).Google Scholar
21 U.S.C. § 331(k).Google Scholar
278 F.3d 926 (9th Cir. 2002).Google Scholar
Kaplan, 836 F.3d at 1209.Google Scholar
Id.Google Scholar
741 F.3d 1314 (D.C. Cir. 2014).Google Scholar
Id. at 1320.Google Scholar
Id. at 1320–21 (citing United States v. Dianovin Pharmaceuticals, Inc., 475 F.2d 100 (1st Cir. 1973)).Google Scholar
Kaplan, 836 F.3d at 1209 (citing United States v. Rhody Dairy, L.L.C., 812 F. Supp. 2d 1239, 1244 (W.D. Wash. 2011)) (“[S]everal cases have held that drugs and devices used in the treatment of patients are ‘held for sale’ by doctors as part of the distribution process.”); see also United States v. Evers, 643 F.2d 1043, 1050 (5th Cir. 1981) (“Doctors holding drugs for use in their practice are clearly one part of the distribution process, and doctors may therefore hold drugs for sale within the meaning of section 301(k) of the Act.”); United States v. Diapulse Corp. of Am., 514 F.2d 1097, 1098 (2d Cir. 1975) (per curiam) (“Such devices, used in the treatment of patients, may properly be considered ‘held for sale’ within the meaning of the [FDCA], 21 U.S.C. § 331(k).”); United States v. Device Labeled “Cameron Spitler Amblyo-Syntonizer,” 261 F. Supp. 243, 246 (D. Neb. 1966) (holding that a physician was not exempt from the requirements of the FDCA when he used misbranded devices in the treatment of his patients even though he did not sell the devices in the commercial sense).Google Scholar
MacIntyre, D.A., Chandiramani, M., and Lee, Y.S. et al., “The Vaginal Microbiome During Pregnancy and the Postpartum Period in a European Population,” Scientific Reports 5 (2015): art. no. 8988.CrossRefGoogle Scholar
Sachs, R.E. and Edelstein, C.A., “Ensuring the Safe and Effective FDA Regulation of Fecal Microbiota Transplantation,” Journal of Law and the Biosciences 2, no. 2 (2015): 396–415.CrossRefGoogle Scholar
Khoruts, A., Hoffmann, D., and Palumbo, F., “The Impact of Regulatory Policies on the Future of Fecal Microbiota Transplantation,” Journal of Law, Medicine & Ethics 47, no. 4 (2019): 482–504.CrossRefGoogle Scholar
Dominguez-Bello, supra note 17.Google Scholar
van der Zande, I.S.E., van der Graaf, R., and Oudijk, M.A. et al., “Vulnerability of Pregnant Women in Clinical Research,” Journal of Medical Ethics 43, no. 10 (2017): 657–663.CrossRefGoogle Scholar
The Nuremburg Code (1949), available at <https://history.nih.gov/research/downloads/nuremberg.pdf> (last visited October 1, 2019).+(last+visited+October+1,+2019).>Google Scholar
The Declaration of Helsinki (1964), available at <https://history.nih.gov/research/downloads/helsinki.pdf> (last visited October 1, 2019).+(last+visited+October+1,+2019).>Google Scholar
45 C.F.R. 46.404, 46.405, 46.406, 46.407.Google Scholar
Microbirth, supra note 38.Google Scholar
Glazer, J., “The Ethics of Alternative Medicine: An Alternative Standard?” Family Practice Management 12, no. 4 (Apr. 2005): 13–14.Google Scholar