Early BCG and Polio Vaccination of Low-Birth-Weight Newborns Lowers Death Risk by 17%

The tuberculosis vaccine BCG and the oral polio vaccine (OPV) have been discussed as having so-called non-specific effects, reducing infections other than their target diseases. The team of Professor B Adhisivam in the Department of Neonatology at JIPMER in India published in the BMJ the results of the BLOW2 trial, which tested whether early vaccination with both vaccines reduces deaths in low-birth-weight newborns under 2 kg.

An open-label randomised controlled trial of 5,420 newborns

At 3 neonatal intensive care units in southeastern India, 5,420 newborns with a birth weight under 2 kg were split 1:1. The early vaccination group (2,714) received an intradermal injection of 0.1 mL of BCG Danish strain and OPV within 48 hours of admission, and the control group (2,706) had vaccination delayed until around discharge. It is an open-label pragmatic trial with no phase designation of the kind used for drug approval. The primary endpoint was death from any cause up to 28 days of life.

Deaths were 238 (8.8%) in the early vaccination group and 273 (10.1%) in the control group, with an adjusted hazard ratio of 0.83 (95% confidence interval 0.69 to 0.98). That works out to 1 death prevented for every 21 newborns vaccinated. Infection-related deaths fell more, with a hazard ratio of 0.53. There were no tuberculosis deaths, and no serious adverse events related to vaccination were reported.

Significance and limitations

The reduction in deaths appeared in non-tuberculosis infection deaths, which supports the hypothesis of non-specific immune effects of the vaccines. However, it was an open trial without blinding, and the infection death measure was added during the trial. The upper bound of the confidence interval is close to 1, and the results are limited to the intensive care unit setting, so they are hard to apply as is to other health care settings.