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Original Investigation
September 15, 2020

Association of Routine Infant Vaccinations With Antibody Levels Among Preterm Infants

Author Affiliations
  • 1Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  • 2Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, the Netherlands
  • 3Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands
JAMA. 2020;324(11):1068-1077. doi:10.1001/jama.2020.12316
Key Points

Question  What is the association between receipt of a routine schedule of vaccinations and subsequent antibody levels among preterm infants over the first year of life?

Findings  In this prospective observational study that included 296 preterm infants and 66 historical control term-born infants, administration of a routine schedule of vaccinations was associated with 95% or more of preterm infants across all gestational ages achieving protective IgG levels for most vaccine antigens on completion of the primary series and the booster dose. However, after the primary series and booster, 40.6% and 88.1% of preterm infants, respectively, achieved protective levels against Haemophilus influenzae type b. In general, postimmunization antibody levels were significantly lower in preterm infants than in the historical control group, with the lowest values in extremely premature infants.

Meaning  Among preterm infants, administration of a routine schedule of vaccinations during the first year was associated with protective antibody levels against most antigens, except for Haemophilus influenzae type b.

Abstract

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.

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