ORIGINAL STUDIES Low Birth Weight Infants and Calmette-Gue ´rin Bacillus Vaccination at Birth Community Study from Guinea-Bissau Adam Roth, MD,† Henrik Jensen, PhD,† May-Lill Garly, MD, PhD,† Queba Djana,* Cesa ´rio Lourenco Martins, MD, MSc,* Morten Sodemann, MD, PhD,* Amabelia Rodrigues, PhD,* and Peter Aaby, MSc† Background: In developing countries, low birth weight (LBW) children are often not vaccinated with Calmette-Gue ´rin bacillus (BCG) at birth. Recent studies have suggested that BCG may have a nonspecific beneficial effect on infant mortality. We evaluated the consequences of not vaccinating LBW children at birth in Guinea- Bissau. Methods: Between 1989 and 1999, 7138 children born at the central hospital had a birth weight registered. We assessed BCG coverage until 3 years of age. Data on tuberculin skin test (TST) for 297 children and BCG scar for 1319 children in the study population were reanalyzed for differences between normal birth weight (NBW) children and LBW children. We assessed the effect of early BCG vaccination on mortality to 12 months of age. Results: Among LBW children there were 1.5- to 3-fold more unvaccinated individuals than among NBW children up to 4 months of age. There was no overall difference between LBW and NBW children in TST or BCG scarring; LBW children vaccinated early may have had slightly reduced reactions to tuberculin. Among 845 LBW children, 182 had received BCG within the first week of life. Controlling for background factors and censoring at first diphtheria- tetanus-pertussis vaccination, measles vaccination or at 6 months of age (whichever came first), the mortality rate ratio for BCG-vacci- nated versus -unvaccinated LBW children was 0.17 (95% confi- dence interval, 0.06 – 0.49), with an even stronger effect for LBW children vaccinated in the first week of life (mortality rate ratio, 0.07; 95% confidence interval, 0.01– 0.62). Conclusions: The policy of not vaccinating with BCG at birth had a negative impact on vaccination coverage for LBW children. Early BCG vaccination had no large negative impact on TST and BCG scarring. Mortality was lower for BCG-vaccinated than for unvac- cinated LBW children controlling for available background factors. BCG vaccination of LBW children may have a beneficial effect on survival that cannot be explained by protection against tuberculosis. Future studies should examine possible adverse effects from equal- izing BCG policy for LBW and NBW children. Key Words: Low birth weight, Calmette-Gue ´rin bacillus, nonspecific effects of vaccination, vaccination policy, infant mortality (Pediatr Infect Dis J 2004;23: 544 –550) T he World Health Organization (WHO) currently recom- mends Calmette-Gue ´rin bacillus (BCG) vaccination at birth in developing countries except for preterm infants who should be vaccinated when they reach the chronologic age of 40 weeks. 1 Because of difficulties in establishing gestational age, vaccination policy for BCG is often defined by birth weight rather than gestational maturity. In Guinea-Bissau, low birth weight (LBW) infants (2500 g) are not vaccinated at birth. The mother is told to return for vaccination when the child has gained sufficient weight, or at 6 weeks of age when the child is supposed to receive the first dose of diphtheria- tetanus-pertussis (DTP) and the second dose of oral polio vaccine. The immune system of premature and LBW infants is impaired. 2 However, only a few and contradictory studies have evaluated the immune response and efficacy of BCG among LBW children. In some studies, BCG-vaccinated premature infants have had poor scar formation and less tuberculin reaction. 3 Other studies found no impairment of Accepted for publication January 26, 2004. From the *Bandim Health Project, Bissau, Guinea-Bissau; and the †Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen, Den- mark. Supported by Novo Nordisk Foundation, the Danish Council for Develop- ment Research, Danish Medical Research, DANIDA; the EU INCO program (ICA4-CT-2001-10095) and The Graduate Research School of International Health at the University of Copenhagen, supported by the Danish Research Academy. P.A. holds a research professorship grant from the Novo Nordisk Foundation. Reprints not available. Copyright © 2004 by Lippincott Williams & Wilkins ISSN: 0891-3668/04/2306-0544 DOI: 10.1097/01.inf.0000129693.81082.a0 The Pediatric Infectious Disease Journal • Volume 23, Number 6, June 2004 544