TY - JOUR
T1 - Rotavirus Vaccine Safety and Effectiveness in Infants With High-Risk Medical Conditions
AU - van Dongen, Josephine A P
AU - Rouers, Elsbeth D M
AU - Schuurman, Rob
AU - Band, Caterina
AU - Watkins, Shannon M
AU - van Houten, Marlies A
AU - Bont, Louis J
AU - Norbruis, Obbe F
AU - Hemels, Marieke A C
AU - van Well, Gijs T J
AU - Vlieger, Arine M
AU - van der Sluijs, Jacqueline
AU - Stas, Helene G
AU - Tramper-Stranders, Gerdien
AU - Kleinlugtenbeld, Elly A
AU - van Kempen, Anne A M W
AU - Wessels, Margreet
AU - van Rossem, Maaike C
AU - Dassel, Carin A C M
AU - Pajkrt, Dasja
AU - Bonten, Marc J M
AU - Bruijning-Verhagen, Patricia C J
N1 - Funding Information:
Members of the RIVAR study team include L.M. Zwart, C. Tims-Polder man, G. van Putten, C. Band and, M. van M Beurden, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. We would also like to thank all RIVAR partici pants and their parents or guardi ans and all research nurses of the different study sites for their contri bution to this project. A special rec ognition to Dr van Werkhoven for assisting on the Bayesian analysis. We thank the Dutch Working Group on Clinical Virology from the Dutch Society for Clinical Microbiology and all participating laboratories for providing the virological data from the weekly Sentinel Surveillance system. Funding sources were the Netherlands Organisation for Health Research and Development (grant number: 836021024), Health care Insurers Innovation Foundation, GlaxoSmithKline Biologicals SA (Study ID: 203108), and University Medical Center Utrecht.
Publisher Copyright:
© 2021 by the American Academy of Pediatrics.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - OBJECTIVES: Rotavirus vaccination has 87% to 100% effectiveness against severe rotavirus acute gastroenteritis (AGE) in healthy infants in high-income countries. Little is known whether infants with medical risk conditions (MRCs) are equally protected and if the vaccine is equally well tolerated. We conducted a quasi-experimental prospective multicenter before-after cohort study to assess the vaccine effectiveness (VE) and safety profile of the human rotavirus vaccine (HRV) among MRC infants that required prolonged or frequent postnatal care.METHODS: The Netherlands has no national rotavirus immunization program, but HRV was implemented in routine care for MRC infants in 13 Dutch hospitals. Participants in the before and after cohort, HRV unvaccinated and vaccinated, respectively, were followed for occurrence of (rotavirus) AGE. VE of at least 1 dose was estimated by using time-to-event analysis for severe rotavirus AGE. Vaccine-related serious adverse event (AEs) after HRV were retrieved systematically from medical charts. Solicited AEs after vaccinations were prospectively collected and compared between vaccination time points with or without HRV.RESULTS: In total, 1482 high-risk infants with MRC were enrolled, including 631 in the before and 851 in the after cohorts; 1302 infants were premature (88.3%), 447 were small for gestational age (30.2%), and 251 had at least 1 congenital disorder (17.0%). VE against severe rotavirus AGE was 30% (95% confidence interval [CI]: -36% to 65%). Overall, the observed number of rotavirus hospitalizations was low and not significantly different between the cohorts (2 and 2, respectively). The rate of vaccine-related serious AE was 0.24 per 100 vaccine doses. The adjusted risk ratio for any AE after HRV vaccination compared with other routine vaccinations was 1.09 (95% CI: 1.05 to 1.12) for concomitant administration and 0.91 (95% CI: 0.81 to 0.99) for single HRV administration. Gastrointestinal AEs were 10% more frequent after HRV.CONCLUSIONS: In contrast to previous findings among healthy term infants, in routine use, HRV offered limited protection to vulnerable medical risk infants. HRV is generally well tolerated in this group in single administration, but when coadministered with routine vaccines, it is associated with higher risk of (mostly gastrointestinal) AE. Our study highlights the importance of studying vaccine performance in subgroups of medically vulnerable infants.
AB - OBJECTIVES: Rotavirus vaccination has 87% to 100% effectiveness against severe rotavirus acute gastroenteritis (AGE) in healthy infants in high-income countries. Little is known whether infants with medical risk conditions (MRCs) are equally protected and if the vaccine is equally well tolerated. We conducted a quasi-experimental prospective multicenter before-after cohort study to assess the vaccine effectiveness (VE) and safety profile of the human rotavirus vaccine (HRV) among MRC infants that required prolonged or frequent postnatal care.METHODS: The Netherlands has no national rotavirus immunization program, but HRV was implemented in routine care for MRC infants in 13 Dutch hospitals. Participants in the before and after cohort, HRV unvaccinated and vaccinated, respectively, were followed for occurrence of (rotavirus) AGE. VE of at least 1 dose was estimated by using time-to-event analysis for severe rotavirus AGE. Vaccine-related serious adverse event (AEs) after HRV were retrieved systematically from medical charts. Solicited AEs after vaccinations were prospectively collected and compared between vaccination time points with or without HRV.RESULTS: In total, 1482 high-risk infants with MRC were enrolled, including 631 in the before and 851 in the after cohorts; 1302 infants were premature (88.3%), 447 were small for gestational age (30.2%), and 251 had at least 1 congenital disorder (17.0%). VE against severe rotavirus AGE was 30% (95% confidence interval [CI]: -36% to 65%). Overall, the observed number of rotavirus hospitalizations was low and not significantly different between the cohorts (2 and 2, respectively). The rate of vaccine-related serious AE was 0.24 per 100 vaccine doses. The adjusted risk ratio for any AE after HRV vaccination compared with other routine vaccinations was 1.09 (95% CI: 1.05 to 1.12) for concomitant administration and 0.91 (95% CI: 0.81 to 0.99) for single HRV administration. Gastrointestinal AEs were 10% more frequent after HRV.CONCLUSIONS: In contrast to previous findings among healthy term infants, in routine use, HRV offered limited protection to vulnerable medical risk infants. HRV is generally well tolerated in this group in single administration, but when coadministered with routine vaccines, it is associated with higher risk of (mostly gastrointestinal) AE. Our study highlights the importance of studying vaccine performance in subgroups of medically vulnerable infants.
KW - Congenital Abnormalities/epidemiology
KW - Controlled Before-After Studies
KW - Female
KW - Gastroenteritis/epidemiology
KW - Hospitalization/statistics & numerical data
KW - Humans
KW - Infant
KW - Infant, Premature
KW - Infant, Small for Gestational Age
KW - Male
KW - Netherlands/epidemiology
KW - Prospective Studies
KW - Rotavirus Infections/epidemiology
KW - Rotavirus Vaccines/administration & dosage
KW - Vaccination Coverage
KW - Vaccine Efficacy
KW - EFFICACY
KW - GASTROENTERITIS
KW - CHILDREN
KW - IMMUNOGENICITY
KW - DISEASE
KW - PREMATURE
KW - BURDEN
U2 - 10.1542/peds.2021-051901
DO - 10.1542/peds.2021-051901
M3 - Article
C2 - 34814164
SN - 0031-4005
VL - 148
JO - Pediatrics
JF - Pediatrics
IS - 6
M1 - 2021051901
ER -