T-cell receptor excision circle levels and safety of paediatric immunization: A population-based self-controlled case series analysis

ABSTRACT

T-cell receptor excision circle levels are a surrogate marker of T-cell production and immune system function. We sought to determine whether non-pathological levels of infant T-cell receptor excision circles were associated with adverse events following immunization. A self-controlled case series design was applied on a sample of 231,693 children who completed newborn screening for severe combined immunodeficiency in Ontario, Canada between August 2013 and December 2015. Exposures included routinely administered pediatric vaccines up to 15 months of age. Main outcomes were combined health services utilization for recognized adverse events following immunization. 1,406,981 vaccination events were included in the final dataset. 103,007 children received the Pneu-C-13 or Men-C-C vaccine and 97,998 received the MMR vaccine at 12 months of age. 67,725 children received the varicella immunization at 15 months. Our analysis identified no association between newborn T-cell receptor excision circle levels and subsequent health services utilization events following DTa-IPV-Hib, Pneu-C-13, and Men-C-C vaccinations at 2-month (RI 0.94[95%CI 0.87-1.02]), 4-month (RI 0.82[95%CI 0.75-0.9]), 6-month (RI 0.63[95%CI 0.57-0.7]) and 12-month (RI 0.49[95%CI 0.44-0.55]). We also found no trends in health services utilization following MMR (RI 1.43[95%1.34-1.52]) or varicella (RI 1.14[95%CI 1.05-1.23]) vaccination. Our findings provide further support for the safety of pediatric vaccinations.

KEYWORDS:

• adverse event following immunization
• vaccine safety
• pediatric immunization
• pediatrics
• immunization
• vaccines

Abbreviations

CIHI	=	Canadian Institute for Health Information
DNA	=	deoxyribonucleic acid
DTaP-IPV-HiB	=	diphtheria, pertussis, tetanus, polio, and Haemophilus influenzae type b vaccine
ED	=	emergency department
ICES	=	Institute for Clinical Evaluative Sciences
MMR	=	measles, mumps, and rubella vaccine
Men-C-C	=	meningococcal C vaccine
MOHLTC	=	Ministry of Health and Long Term Care
OHIP	=	Ontario health insurance plan
Pneu-C-13	=	13-valent pneumococcal conjugate vaccine
RIR	=	relative incidence ratio
Rot-1	=	rotavirus vaccine
SCID	=	severe combined immunodeficiency
SCCS	=	self-controlled case series
TREC	=	T-cell receptor excision circle
Var	=	varicella

Disclosure of potential conflicts of interest

The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. JL holds a tier 1 Canada Research Chair.

Data statement

The data used in this study are available with permission from the Institute for Clinical Evaluative Sciences.

Other

There are no prior publications or submissions with any overlapping information, including studies and patients.

Additional information

Funding

This study was supported by a Grand Challenges Explorations grant from the The Bill & Melinda Gates Foundation [OPP1141535]. This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC).