Immediate Bacille Calmette-Guérin Vaccination to Neonates Requiring Perinatal Treatment at the Maternity Ward in Guinea-Bissau: A Randomized Controlled Trial.

BACKGROUND: Randomized controlled trials (RCTs) indicate that bacille Calmette-Guérin (BCG) vaccination provides broad beneficial "nonspecific" protection against infections. We investigated the effect on in-hospital mortality of providing BCG immediately upon admission to a neonatal intensive care unit (NICU), rather than BCG-at-discharge. The pretrial NICU mortality was 13% and we hypothesized that BCG would reduce mortality by 40%. METHODS: Parallel-group, open-label RCT was initiated in 2013 in Guinea-Bissau. Neonatal intensive care unit-admitted neonates were randomized 1:1 to BCG + oral polio vaccine (OPV) immediately (intervention) versus BCG + OPV at hospital discharge (control; usual practice). The trial was discontinued due to decreasing in-hospital mortality and major NICU restructuring. We assessed overall and disease-specific mortality by randomization allocation in cox proportional hazards models providing mortality rate ratios (MRRs). RESULTS: We recruited 3353 neonates, and the overall mortality was 3.1% (52 of 1676) for BCG-vaccinated neonates versus 3.3% (55 of 1677) for controls (MRR = 0.94; 0.64-1.36). For noninfectious causes of death, the MRR was 1.20 (0.70-2.07), and there tended to be fewer deaths from infections in the BCG group (N = 14) than among controls (N = 21) (MRR = 0.65; 0.33-1.28). CONCLUSIONS: Providing BCG + OPV to frail neonates was safe and might protect against fatal infection in the immediate newborn period. Deaths due to prematurity and perinatal complications were unaffected by BCG.

Admission and mortality at the main neonatal intensive care unit in Guinea-Bissau.

Background: The authors assessed the risk of admission and mortality at the main neonatal intensive care unit (NICU) at the National Hospital Simão Mendes (NHSM) in Guinea-Bissau. Methods: The Bandim Health Project (BHP) maintains a health and demographic surveillance system (HDSS) in the capital Bissau, including at the NHSM. Data from January 2008 to August 2013 was used to assess NICU incubator admissions and mortality. Results: The overall NICU admission rate was 4.8% (1575/33,005); the lowest rate in 2012 (4.0% (214/5293)) and the highest rate in 2009 (6.0% (369/6134)). The overall mortality among admitted children was 19.6% (289/1476), declining from 26.7% (68/255) in 2008 to 13.0% (16/123) in 2013. Birth weight <1500 g (OR=353, (95% CI: 244-510) compared with normal birth weight 2500 g-4000 g), Apgar score≤3 (OR=13.2 (9.72-18.0) compared with Apgar score 7-10) and single motherhood (OR=1.44 (1.20-1.74)) were associated with NICU admission. Low Apgar score was a risk factor for NICU mortality (OR=6.21 (2.05-18.81)) and females (OR=0.55 (0.38-0.79) had a lower mortality than males. Conclusion: Approximately 5% of the hospital-born children were admitted to an incubator and among those almost 20% died, although mortality did decline. Male sex, very low birth weight and low Apgar score were strongly associated with NICU admissions and mortality.

Neonatal vitamin A supplementation associated with a cluster of deaths and poor early growth in a randomised trial among low-birth-weight boys of vitamin A versus oral polio vaccine at birth.

BACKGROUND: The effect of oral polio vaccine administered already at birth (OPV0) on child survival was not examined before being recommended in 1985. Observational data suggested that OPV0 was harmful for boys, and trials have shown that neonatal vitamin A supplementation (NVAS) at birth may be beneficial for boys. We set out to test this research question in a randomised trial. METHODS: The trial was carried out at the Bandim Health Project, Guinea-Bissau. We planned to enrol 900 low-birth weight (LBW) boys in a randomised trial to investigate whether NVAS instead of OPV0 could lower infant mortality for LBW boys. At birth, the children were randomised to OPV (usual treatment) or VAS (intervention treatment) and followed for 6 months for growth and 12 months for survival. Hazard Ratios (HR) for mortality were calculated using Cox regression. We compared the individual anthropometry measurements to the 2006 WHO growth reference. We compared differences in z-scores by linear regression. Relative risks (RR) of being stunted or underweight were calculated in Poisson regression models with robust standard errors. RESULTS: In the rainy season we detected a cluster of deaths in the VAS group and the trial was halted immediately with 232 boys enrolled. The VAS group had significantly higher mortality than the OPV0 group in the rainy season (HR: 9.91 (1.23 - 80)). All deaths had had contact with the neonatal nursery; of seven VAS boys enrolled during one week in September, six died within two months of age, whereas only one died among the six boys receiving OPV (p = 0.05). Growth (weight and arm-circumference) in the VAS group was significantly worse until age 3 months. CONCLUSION: VAS at birth instead of OPV was not beneficial for the LBW boys in this study. With the premature closure of the trial it was not possible to answer the research question. However, the results of this study call for extra caution when testing the effect of NVAS in the future. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00625482. Registered 18 February 2008.

The effect of neonatal vitamin A supplementation on growth in the first year of life among low-birth-weight infants in Guinea-Bissau: two by two factorial randomised controlled trial.

BACKGROUND: Vitamin A supplementation (VAS) may amplify the effect of vaccines. We therefore investigated if neonatal VAS given with and without Bacille Calmette-Guérin (BCG) vaccine to low-birth-weight (LBW) neonates had an effect on growth in the first year of life. We hypothesised that VAS would be particularly beneficial when provided with BCG. METHODS: We conducted a randomised two-by-two factorial trial in Guinea-Bissau; 1,717 LBW neonates were randomly allocated to VAS or placebo at birth as well as early or the usual postponed BCG vaccination. Anthropometric measurements were obtained at 2, 6, and 12 months after inclusion. RESULTS: Overall there was no effect of neonatal VAS on growth in the first year of life. By 2 months, VAS tended to have a beneficial effect on weight and head circumference when given with BCG but not when given without BCG (interaction: weight-for-age p = 0.07 and head circumference-for-age: p = 0.06). By 6 months, there was a beneficial effect of VAS on head circumference and weight among children who had not received DTP vaccine 2 months after inclusion (weight: 0.18 (0.00; 0.36) and head circumference 0.27 (0.06; 0.48)), but no beneficial effect among those who had received DTP. CONCLUSION: The results support other trials indicating that neonatal VAS does not have consistent effects on childhood growth and if anything the effects seem to be temporary. They also show that the effect may differ by vaccination status, being beneficial when given with BCG at birth and when DTP is delayed. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT00168610).

A prospective study of twinning and perinatal mortality in urban Guinea-Bissau.

BACKGROUND: Despite twinning being common in Africa, few prospective twin studies have been conducted. We studied twinning rate, perinatal mortality and the clinical characteristics of newborn twins in urban Guinea-Bissau. METHODS: The study was conducted at the Bandim Health Project (BHP), a health and demographic surveillance site in Bissau, the capital of Guinea-Bissau. The cohort included all newborn twins delivered at the National Hospital Simão Mendes and in the BHP study area during the period September 2009 to August 2011 as well as singleton controls from the BHP study area. Data regarding obstetric history and pregnancy were collected at the hospital. Live children were examined clinically. For a subset of twin pairs zygosity was established by using genetic markers. RESULTS: Out of the 5262 births from mothers included in the BHP study area, 94 were twin births, i.e. a community twinning rate of 18/1000. The monozygotic rate was 3.4/1000. Perinatal mortality among twins vs. singletons was 218/1000 vs. 80/1000 (RR = 2.71, 95% CI: 1.93-3.80). Among the 13783 hospital births 388 were twin births (28/1000). The hospital perinatal twin mortality was 237/1000.Birth weight < 2000g (RR = 4.24, CI: 2.39-7.51) and caesarean section (RR = 1.78, CI: 1.06-2.99) were significant risk factors for perinatal twin mortality. Male sex (RR = 1.38, CI: 0.97-1.96), unawareness of twin pregnancy (RR = 1.64, CI: 0.97-2.78) and high blood pressure during pregnancy (RR = 1.77, CI: 0.88-3.57) were borderline non-significant. Sixty-five percent (245/375) of the mothers who delivered at the hospital were unaware of their twin pregnancy. CONCLUSIONS: Twins had a very high perinatal mortality, three-fold higher than singletons. A birth weight < 2000g was the strongest risk factor for perinatal death, and unrecognized twin pregnancy was common. Urgent interventions are needed to lower perinatal twin mortality in Guinea-Bissau.