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In this systematic review and meta-analysis of evidence-based interventions to reduce mortality among preterm and low birthweight (LBW) neonates in low-income and middle-income countries, the implementation of four effective interventions in current WHO guidelines is encouraged: cord and skin cleansing with chlorhexidine, community kangaroo mother care, home-based new-born care and early Bacille Calmette-Guérin (BCG) vaccination.
Regarding BCG vaccination, the authors identified two randomised controlled trials (RCTs) of BCG-Denmark vs. no-BCG to LBW neonates and estimated that providing early BCG reduces neonatal mortality by 36% (14% to 52%). In addition to the two trials, a small RCT of BCG-Denmark to LBW neonates reported an effect estimate of 0.28 (0.06 to 1.37). In a combined analysis of the three datasets, providing early BCG-Denmark to LBW neonates at hospital discharge was associated with a 38% (17% to 54%) reduction in neonatal mortality. Also, a recent Ugandan RCT of BCG-Denmark vs. no-BCG found BCG-Denmark associated with fewer early-life infections, particularly for LBW, further strengthening the argument for using BCG-Denmark as an evidence-based intervention for LBW neonates.
Many manufacturers produce BCG world-wide, and the genetically different BCG strains might not have the same effects on all-cause mortality. For example, two RCTs conducted in India evaluated the effects of providing BCG-Russia vs. no-BCG to a cohort of neonates...
Many manufacturers produce BCG world-wide, and the genetically different BCG strains might not have the same effects on all-cause mortality. For example, two RCTs conducted in India evaluated the effects of providing BCG-Russia vs. no-BCG to a cohort of neonates weighing <2000 g that were admitted for intensive care. In the two frail cohorts with a high overall mortality of 17% but few infectious disease deaths, BCG-Russia had no effect on in-hospital all-cause mortality, the combined hazard ratio being 0.98 (0.85 to 1.11).
It is not known whether the lack of an effect in the India RCTs was due to the use of BCG-Russia rather than BCG-Denmark or the frailty of the cohorts (lower-weight neonates admitted for intensive care treatment with a high mortality risk mainly from perinatal complications rather than infection). Either way, it deserves to be emphasized that the current evidence supports that providing early BCG-Denmark at discharge is associated with reduced neonatal mortality risk from infectious diseases.
Providing immunogenic BCG strains early is also associated with improved long-term survival; in a cohort of neonates vaccinated within 1 week of life, we showed that having a BCG skin reaction by 2 months of age is associated with a 51% (5% to 74%) reduced mortality between 2-12 months of age. Also, there was a linear trend of decreasing mortality with increasing reaction size.
Unfortunately, BCG is often delayed; in rural Africa more than half of children are not vaccinated within the first month of life due to regulations to restrict vial-dose wastage, antiquated guidelines of not vaccinating LBW neonates and logistical hurdles. New WHO guidelines emphasising immunogenic BCG strains as a life-saving intervention provided at birth and the assessment of BCG vaccination coverage by 1 months of age as a vaccine program indicator would help increase its early deployment and impact.