Vaginal Delivery and Breastfeeding Benefit Infant Immune Response to Hepatitis B Vaccine: A Prospective Cohort Study

Background and Aims Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants, and the immune response of infants to vaccines is closely related to their immune system. This large prospective cohort study aimed to explore the effects of delivery and feeding mode on infant’s immune response to hepatitis B vaccine (HepB). Methods A total of 1,254 infants who completed the whole course of HepB immunization and whose parents were both HBsAg negative were enrolled from infants born in Jinchang City during 2018–2019 by cluster sampling method. Results Twenty (1.59%) of the 1,254 infants were nonresponders to HepB. Among the other 1,234 infants, 10.05% (124/1,234), 81.69% (1,008/1,234) and 8.27% (102/1,234) of infants had low, medium, and high responses to HepB, respectively. Logistic regression analysis showed that cesarean section (OR: 8.58, 95% CI: 3.11–23.65, p<0.001) and birth weight <3.18 kg (OR: 5.58, 95% CI: 1.89–16.51, p=0.002) were independent risk factors for infant nonresponse to HepB, and cesarean section (OR: 7.63, 95% CI: 4.64–12.56, p<0.001), formula feeding (OR: 4.91, 95% CI: 1.47–16.45, p=0.001), maternal anti-HBs negativity (OR: 27.2, 95% CI: 10.67–69.35, p<0.001), paternal non-response history of HepB (OR: 7.86, 95% CI: 2.22–27.82, p=0.014) and birth weight <3.22 kg (OR: 4.00, 95% CI: 2.43–6.59, p<0.001) were independent risk factors for infant low response to HepB. In cases where birth weight and genetic factors are unmodifiable and maternal anti-HBs effects are controversial, it makes sense to enhance infant response by changing delivery and feeding patterns. Conclusions Natural vaginal delivery and breastfeeding are beneficial to the infant’s immune response to HepB.

[1]  Suping Wang,et al.  Infant immune response to hepatitis B vaccine after fetal exposure to telbivudine , 2022, Human vaccines & immunotherapeutics.

[2]  S. Choukem,et al.  Immune response to hepatitis B vaccine following complete immunization of children attending two regional hospitals in the Southwest region of Cameroon: a cross sectional study , 2021, BMC Infectious Diseases.

[3]  Xu-hui Zhang,et al.  The optimal interval for post-vaccination serological test in infants born to mothers with positive hepatitis B surface antigen , 2021, Human vaccines & immunotherapeutics.

[4]  M. Jiang,et al.  Anti-HBs levels in children under the age of two years born to HBV carrier mothers after immunoprophylaxis: a multicenter cross-sectional study , 2021, BMC Pediatrics.

[5]  R. Cole,et al.  Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model , 2021, Frontiers in Cell and Developmental Biology.

[6]  E. Claud,et al.  Childhood Development and the Microbiome: The Intestinal Microbiota in Maintenance of Health and Development of Disease During Childhood Development. , 2020, Gastroenterology.

[7]  W. D. de Vos,et al.  Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study , 2020, Cell.

[8]  B. Pulendran,et al.  The Impact of the Microbiome on Immunity to Vaccination in Humans , 2020, Cell Host & Microbe.

[9]  M. Y. Zeng,et al.  Neonatal gut microbiome and immunity. , 2020, Current opinion in microbiology.

[10]  S. K. Maurya,et al.  Gut Dysbiosis Thwarts the Efficacy of Vaccine Against Mycobacterium tuberculosis , 2020, Frontiers in Immunology.

[11]  Shengli Bi,et al.  Long-term protection at 20–31 years after primary vaccination with plasma-derived hepatitis B vaccine in a Chinese rural community , 2020, Human vaccines & immunotherapeutics.

[12]  M. Stares,et al.  Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth , 2019, Nature.

[13]  B. Pulendran,et al.  Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans , 2019, Cell.

[14]  N. Curtis,et al.  Factors That Influence the Immune Response to Vaccination , 2019, Clinical Microbiology Reviews.

[15]  K. Kalanetra,et al.  Bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age , 2019, Pediatrics.

[16]  A. Gasbarrini,et al.  What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases , 2019, Microorganisms.

[17]  F. Barros,et al.  Global epidemiology of use of and disparities in caesarean sections , 2018, The Lancet.

[18]  N. Curtis,et al.  The influence of the intestinal microbiome on vaccine responses. , 2018, Vaccine.

[19]  D. Lynn,et al.  Early-Life Antibiotic-Driven Dysbiosis Leads to Dysregulated Vaccine Immune Responses in Mice. , 2018, Cell host & microbe.

[20]  Y. Shoenfeld,et al.  Breastfeeding and autoimmunity: Programing health from the beginning , 2018, American journal of reproductive immunology.

[21]  W. D. de Vos,et al.  The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota , 2017, Microbiology and Molecular Biology Reviews.

[22]  W. D. de Vos,et al.  Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan , 2017, Gut microbes.

[23]  Zhenyu Yang,et al.  Breastfeeding rates in China: a cross-sectional survey and estimate of benefits of improvement , 2016, The Lancet.

[24]  B. McMahon,et al.  A Longitudinal Hepatitis B Vaccine Cohort Demonstrates Long-lasting Hepatitis B Virus (HBV) Cellular Immunity Despite Loss of Antibody Against HBV Surface Antigen. , 2016, The Journal of infectious diseases.

[25]  J. Clemente,et al.  The microbiome in early life: implications for health outcomes , 2016, Nature Medicine.

[26]  B. McMahon,et al.  Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose. , 2016, The Journal of infectious diseases.

[27]  Hongzhe Li,et al.  Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants. , 2016, JAMA pediatrics.

[28]  Lonny Henriksen,et al.  Cesarean section and disease associated with immune function. , 2016, The Journal of allergy and clinical immunology.

[29]  M. Nassal.  HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B , 2015, Gut.

[30]  V. Tremaroli,et al.  Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. , 2015, Cell host & microbe.

[31]  Jun Zhang,et al.  Use of the Robson classification to assess caesarean section trends in 21 countries: a secondary analysis of two WHO multicountry surveys. , 2015, The Lancet. Global health.

[32]  Ling Zhang,et al.  Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine. , 2014, Vaccine.

[33]  K. Kalanetra,et al.  Stool Microbiota and Vaccine Responses of Infants , 2014, Pediatrics.

[34]  J. Li,et al.  Maternal immunization promotes the immune response of neonates towards hepatitis B vaccine , 2013, Journal of viral hepatitis.

[35]  Anders F. Andersson,et al.  Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section , 2013, Gut.

[36]  Yonghui Zhang,et al.  Revaccination of non- and low- responders after a standard three dose hepatitis B vaccine schedule , 2012, Human vaccines & immunotherapeutics.

[37]  Yali Hu,et al.  Transplacentally Acquired Maternal Antibody against Hepatitis B Surface Antigen in Infants and its Influence on the Response to Hepatitis B Vaccine , 2011, PloS one.

[38]  R. Minamisava,et al.  Presence of maternal anti-HBs antibodies does not influence hepatitis B vaccine response in Brazilian neonates. , 2011, Memorias do Instituto Oswaldo Cruz.

[39]  Ding‐Shinn Chen.  Hepatitis B vaccination: The key towards elimination and eradication of hepatitis B. , 2009, Journal of hepatology.

[40]  R. Rüttimann,et al.  Immunogenicity and reactogenicity of DTPa‐HBV‐IPV/Hib vaccine as primary and booster vaccination in low‐birth‐weight premature infants , 2008, Acta paediatrica.

[41]  A. Ersbøll,et al.  T‐lymphocyte subsets, thymic size and breastfeeding in infancy , 2004, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[42]  K. Michaelsen,et al.  Decreased thymus size in formula‐fed infants compared with breastfed infants , 1996, Acta paediatrica.

[43]  H. Steward.  Responses , 1991, Problems and Perspectives of Conventional Disarmament in Europe.

[44]  G. Moro,et al.  Antibody Responses to Parenteral and Oral Vaccines Are Impaired by Conventional and Low Protein Formulas as Compared to Breast‐feeding , 1990, Acta paediatrica Scandinavica.

[45]  E. Dempsey,et al.  Maternal Vertical Transmission Affecting Early-life Microbiota Development. , 2019, Trends in microbiology.