title: Impact of withholding breastfeeding at the time of vaccination on the immunogenicity of oral rotavirus vaccine--a randomized trial.
abstract: BACKGROUND
  Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration.
  
  
  METHODS
  Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥ 20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective).
  
  
  RESULTS
  Four hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p = 0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p = 0.005).
  
  
  CONCLUSIONS
  Withholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a breastfeed at the time of vaccination. On the contrary, IgA seroconversion in infants immediately breastfed tended to be higher than in those withheld from a feeding. Our findings suggest that breastfeeding should be continued adlib around the time of rotavirus vaccination and withholding breastfeeding at that time is unlikely to improve the vaccine immunogenicity.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01199874.
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
authors.forename: Asad
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
authors.forename: Abdul Momin
authors.initials: AM
authors.lastname: Kazi
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Cortese
authors.affiliation: Vaccine Access and Delivery, Program for Appropriate Technology in Health (PATH), Seattle, WA, United States of America.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Fleming
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: SungSil
authors.initials: S
authors.lastname: Moon
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Parashar
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Baoming
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
authors.forename: Monica M
authors.initials: MM
authors.lastname: McNeal
authors.affiliation: Vaccine Access and Delivery, Program for Appropriate Technology in Health (PATH), Seattle, WA, United States of America.
authors.forename: Duncan
authors.initials: D
authors.lastname: Steele
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
authors.forename: Zulfiqar
authors.initials: Z
authors.lastname: Bhutta
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
authors.forename: Anita K M
authors.initials: AK
authors.lastname: Zaidi
mesh_terms: D000284:Administration, Oral; D001942:Breast Feeding; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008895:Milk, Human / Q000276:immunology; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D007070:Immunoglobulin A; C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated