Safety and Immunogenicity of Early Bacillus Calmette-Guérin Vaccination in Infants Who Are Preterm and/or Have Low Birth Weights : A Systematic Review and Meta-analysis

Key Points

Question

Is administration of bacillus Calmette-Guérin (BCG) vaccination within 7 days of birth safe, immunogenic, and efficacious in infants who are preterm and/or have low birth weight, compared with BCG vaccination at later points or in infants who are normal birth weight?

Findings

In this systematic review and meta-analysis, we found no increase in adverse reactions or infant mortality after BCG vaccination within 7 days of birth compared with vaccination delayed after 7 days in clinically stable infants who were preterm and/or had low birth weight. Meta-analysis revealed no differences for scar formation or tuberculin skin test conversion.

Meaning

Currently, evidence from clinically stable infants who were born after more than 30 weeks’ gestational age and/or weighing more than 1.5 kg seems to support BCG vaccination within 7 days of birth.

Abstract

This systematic review and meta-analysis examines the safety and efficacy of bacillus Calmette-Guérin vaccination at birth or later points in infants who are preterm and/or had low birth weights compared with ones who are full term and/or had normal birth weights.

Abstract

Importance

Bacillus Calmette-Guérin (BCG) vaccination is commonly delayed in infants who are preterm and have low birth weights (LBW) despite the association of early vaccination with better vaccination coverage and potentially nonspecific benefits for survival.

Objective

To determine the safety, immunogenicity, and protective efficacy against tuberculosis (TB) of BCG vaccination given at or before 7 days after birth vs vaccination more than 7 days after birth among infants who are preterm and/or had LBW.

Data Sources

Searches of Medline, Embase, and Global Health databases were conducted from inception until August 8, 2017.

Study Selection

Clinical trials, cohort studies, and case-control studies that included infants who were preterm and/or had LBW and reported safety, mortality, immunogenicity, proxies of vaccine take, and/or efficacy against TB.

Data Extraction and Synthesis

Two authors independently extracted data and assessed the quality of the studies. Data extracted included demographics, covariates, sources of bias, and effect estimates. Meta-analysis was performed using a random-effects model.

Main Outcomes and Measures

Safety, mortality, immunogenicity, or other proxies of vaccine take, such as tuberculin skin test (TST) conversion and efficacy against tuberculosis.

Results

Forty studies were included in a qualitative synthesis; infants who were preterm (born at 26-37 weeks’ gestational age) and/or had LBW (0.69-2.5 kg at birth) were included. The BCG vaccine was administered at or before 7 days to 10 568 clinically stable infants who were preterm and/or had LBW; vaccination was administered to 4310 infants at varying times between 8 days and 12 months after birth. Twenty-one studies reporting safety found no cases of BCG-associated death or systemic disease in 8243 infants. Four studies reported no increase in all-cause mortality for infants who had LBW and who received early BCG vaccination compared with infants who had LBW with later vaccination or BCG-vaccinated infants of normal birth weight. Four studies reported lymphadenitis incidence; combined, these reported 0% to 2.9% incidence of vaccination within 7 days and 0% to 4.2% of vaccination after 7 days. Meta-analysis of 7 studies revealed no differences between early and delayed BCG vaccination for scar formation (n = 515; relative risk [RR], 1.01 [95% CI, 0.95-1.07]) or TST conversion (n = 397; RR, 0.97 [95% CI, 0.84-1.13]). Published data were insufficient to assess immunogenicity or protective efficacy against TB disease.

Conclusions and Relevance

Early BCG vaccination in healthy infants who are preterm and/or had LBW has a similar safety profile, reactogenicity, and TST conversion rate as delayed vaccination. Based on current evidence, early BCG vaccination in stable infants who are preterm and/or have LBW to optimize uptake is warranted.