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Objective To examine the association between early Bacille Calmette-Guerin (BCG) vaccination and neonatal mortality in northern Ghana Methods This ecological study used vaccination and mortality data from the Navrongo Health and Demographic Surveillance System First, we assessed and compared changes in neonatal mortality rates (NMRs) and median BCG vaccination age from 1996 to 2012 Second, we compared the changes in NMR and median BCG vaccination age from 2002 to 2012 by delivery place when data on delivery place were available Results Neonatal mortality rates declined from 46 to 12 per 1000 live births between 1996 and 2012 (trend test: P<0001) Within the same period, median BCG vaccination age declined from 46 to 4 days (trend test: P<0001) Among home deliveries, BCG vaccination age declined from 39 days in 2002 to 7 days in 2012 (trend test: P<0001) and neonatal mortality declined by 24/1000 (trend test: P<0001) Among health facility deliveries, BCG vaccination age was stable around 3 days from 2002 to 2012 (trend test: P=049) and neonatal mortality declined by 9/1000 (trend test: P=004) In a small study of children whose vaccination cards were inspected within the first 28 days of life, the HR for BCG-vaccinated compared with BCG-unvaccinated children was 055 (95% CI 012 to 240) Conclusion The data support the hypothesis that early BCG vaccination may be associated with a decrease in neonatal mortality However, as suggested by WHO, randomised control trials are required to address the question of whether there is indeed a causal association between early BCG vaccination and neonatal mortality.
The study was conducted in the Kassena-Nankana East municipal and Kassena-Nankana West district in the Upper East region of northern Ghana with an estimated population of about 160 000 under continuous demographic surveillance. The study area covers a land area of 1675 km2 and lies between latitude 10.30o and 11.10o north and longitude 1.10o west close to the Burkina Faso border. It has 1 main hospital (War Memorial Hospital) that serves as a referral hospital to nine clinics or health centres and 45 Community Health Compounds located mostly in rural communities and manned by trained nurses who provide basic healthcare as well as routine vaccinations. Previous analysis of causes of neonatal deaths in the study area showed that 32% of the causes were from infections, 21% from birth injury and asphyxia and 18% from prematurity, making these three the leading causes of neonatal deaths in the area.12 Routine vaccination data from 1996 to 2012 collected by the Navrongo HDSS were used for the analyses.13 14 Between 1996 and 2010, vaccination data were collected once annually from health cards of children <2 years of age, except in 2001 when the HDSS failed to collect vaccination data. From 2011 to 2012, vaccination data were updated every 4 months for children aged 3 years or younger. The HDSS field teams visited all households 3–4 times a year during the period of the study from 1996 to 2012 to document demographic events such as new births, deaths and migrations. Data on educational attainment and household possessions are documented as part of the HDSS operations. Even though Ghana introduced routine BCG vaccination into its EPI programme in 1978, accurate data on BCG strains used in Ghana from 1978 to 2006 are not available.15 The following BCG strains were used for vaccination in Ghana: 2007, BCG-Danish, produced by Danish Statens Serum Institute; 2008 to 2009, the BCG-Russia, produced by Bulbio; and from 2010 to 2012, BCG-Japan, produced by Japan BCG Laboratory.15 Data were analysed using STATA V.12.1. To assess the association between median BCG vaccination age and neonatal mortality, we calculated yearly neonatal mortality rates (NMRs) per 1000 live births for children born in the study area from 1996 to 2012. We also calculated median BCG vaccination age by birth year from 1996 to 2012. Trends in NMR and median BCG vaccination age were assessed to identify any association for children delivered in health facilities and at home, respectively. We carried out an individual-level analysis of children delivered at home and visited in the first 28 days of life using a Cox regression model to examine any association between their BCG vaccination status and subsequent neonatal mortality. We adjusted for socioeconomic status (wealth index), sex, maternal age, maternal education, interview year and season of birth. The wealth index was computed using principal component analysis from household assets as an estimate of household socioeconomic status. The household assets included several separate items, from large to medium assets (eg, land, car and motorbike ownership) to smaller household items (eg, radio, fan ownership). The children were categorised into BCG-vaccinated and BCG-unvaccinated based on BCG vaccination status in their health cards. Children with health cards and recorded BCG vaccination dates were classified as BCG-vaccinated. Those with no health card or no record of BCG vaccination on their vaccination card were categorised as BCG-unvaccinated. Children whose vaccination cards were not seen or those we did not meet at the time of the home visit were excluded from the substudy analysis. There was no loss to follow-up in the individual-level study. The exposure data (vaccination status) were collected before the occurrence of the outcome for all participants. The criterion for inclusion was that a child should first be visited and be alive at the time of the visit in the first 28 days after birth. It was only in subsequent visits that an outcome could be assessed. The exposure data (vaccination) and the outcome data (survival) were independently collected, in most cases, by different fieldworkers. Virtually all deliveries in health facilities were vaccinated, and we did not have complete data on delivery place for the entire period of the study. Data on place of delivery were only available from 2002. In addition, other background characteristics including access to healthcare of the children delivered in health facilities, which we could not measure in this study, may be different from those delivered at home. We therefore limited the analysis to home deliveries, which are likely to have the same background characteristics including health-seeking behaviour and access to healthcare. To reduce survival bias,16 neonatal mortality was assessed prospectively using the landmark approach from the date of visit until the child was 28 days of age. Survival bias leads to differential misclassification of vaccine status because children who survive have better information than those who died during follow-up because health cards for dead children were often not available for inspection. With incomplete vaccine information for dead children, vaccination becomes automatically associated with a strong beneficial effect. In the landmark approach, only vaccine information collected on the date of visit is used, and the vaccine status becomes a time-fixed variable during follow-up in the analysis. This approach gives conservative estimates.16 Patients were not involved in developing the hypothesis, the specific objectives or the research questions. They were also not involved in the design of the survey instruments or conduct of the study. No patients were involved in the interpretation of study results or write up of the manuscript. There are no plans to disseminate the results of the research to study participants or the relevant study community.
