Association of Routine Infant Vaccinations with Antibody Levels among Preterm Infants

Elsbeth D.M. Rouers*, Patricia C.J. Bruijning-Verhagen, Pieter G.M. Van Gageldonk, Josephine A.P. Van Dongen, Elisabeth A.M. Sanders, Guy A.M. Berbers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Importance: The standard schedule of national immunization programs for infants may not be sufficient to protect extremely and very preterm infants. Objective: To evaluate the immunogenicity of routine vaccinations administered to preterm infants. Design, Setting, and Participants: A multicenter, prospective, observational cohort study of preterm infants stratified according to gestational age recruited from 8 hospitals across the Netherlands between October 2015 and October 2017, with follow-up until 12 months of age (October 2018). In total, 296 premature infants were enrolled and compared with a control group of 66 healthy term infants from a 2011 study, immunized according to the same schedule with the same vaccines. Exposures: Three primary doses of the diphtheria-tetanus toxoids-acellular pertussis-inactivated poliomyelitis-Haemophilus influenza type b-hepatitis B combination vaccine were given at 2, 3, and 4 months after birth followed by a booster at 11 months and a 10-valent pneumococcal conjugate vaccine at 2, 4, and 11 months after birth. Main Outcomes and Measures: Primary end points were (1) proportion of preterm infants who achieved IgG antibody against vaccine antigens at concentrations above the internationally defined threshold for protection after the primary series and booster dose and (2) serum IgG geometric mean concentrations after the primary series and booster vaccination. Proportions and geometric mean concentrations were compared in preterm infants and the control group of term infants. Results: Of 296 preterm infants (56.1% male; mean gestational age, 30 weeks), complete samples before vaccination, 1 month after the primary series, and 1 month after the booster were obtained from 220 preterm infants (74.3%). After the primary series, the proportion of preterm infants across all gestational age groups who achieved protective IgG antibody levels against pertussis toxin, diphtheria, tetanus and 6 of 10 pneumococcal serotypes varied between 83.0% and 100%, Haemophilus influenzae type b between 34.7% and 46.2% (40.6% among all preterm infants overall), and pneumococcal serotypes 4, 6B, 18C, and 23F between 45.8% and 75.1%. After the booster dose, protective antibody levels were achieved in more than 95% of all preterm groups, except for Haemophilus influenzae type b (88.1%). In general, geometric mean concentrations of all vaccine-induced antibodies were significantly lower in all preterm infants vs term infants, except for pertussis toxin and pneumococcal serotypes 4 and 19F after the primary series and booster vaccination. Conclusions and Relevance: Among preterm infants, administration of routine vaccinations during the first year of life was associated with protective antibody levels against most antigens in the majority of infants after the primary series and booster, except for Haemophilus influenzae type b. However, antibody concentrations were generally lower among preterm infants compared with historical controls..

Original languageEnglish
Pages (from-to)1068-1077
Number of pages10
JournalJAMA - Journal of the American Medical Association
Issue number11
Publication statusPublished - 15 Sept 2020


  • Antibodies, Bacterial/blood
  • Antibodies, Viral/blood
  • Cohort Studies
  • Diphtheria-Tetanus-Pertussis Vaccine/immunology
  • Female
  • Haemophilus Vaccines/immunology
  • Historically Controlled Study
  • Humans
  • Immunization, Secondary
  • Immunoglobulin G/blood
  • Infant
  • Infant, Premature/immunology
  • Male
  • Pneumococcal Vaccines/immunology
  • Poliovirus Vaccine, Inactivated/immunology
  • Vaccines, Conjugate/immunology
  • Vaccines/immunology


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