Article

Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: Two by two factorial randomised controlled trial

Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
BMJ (online) (Impact Factor: 17.45). 03/2010; 340(mar09 1):c1101. DOI: 10.1136/bmj.c1101
Source: PubMed

ABSTRACT

To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates.
Randomised, placebo controlled, two by two factorial trial.
Bissau, Guinea-Bissau.
1717 low birthweight neonates born at the national hospital.
Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months.
Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo.
No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation being 0.74 (95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau, the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 (95% CI 0.87 to 1.33); 0.80 (95% CI 0.58 to 1.10) in boys and 1.41 (95% CI 1.04 to 1.90) in girls (P=0.01 for interaction between neonatal vitamin A and sex).
The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that, overall, it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau. Worryingly, the trials show that vitamin A supplementation at birth can be harmful in girls. Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects. Trial registration ClinicalTrials.gov NCT00168610.

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    • "In 2004 in Guinea-Bissau, two randomized trials were ongoing, testing the effect of neonatal vitamin A supplementation in normal-birth-weight children and the effect of BCG at birth to lowbirth-weight children, respectively [4] [5]. That year the country experienced periods when OPV was in short supply. "
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    ABSTRACT: Background In Guinea-Bissau we conducted a randomized trial of OPV0 versus No OPV0 to test the effect of not receiving OPV0 on infant mortality and morbidity. In two subgroups of participants, 6-week-old children and 6-month-old children, we investigated the effect of OPV0 on neutralizing antibodies against poliovirus type 1 and 3. Design A subgroup of infants randomized to receive OPV0 or No OPV0 in addition to the usual childhood vaccines were visited at home at 6 weeks or 6 months of age, and a blood sample was collected from the child and the mother. Setting Urban Guinea-Bissau. Main outcome Geometric mean titers (GMT) of neutralizing antibodies and seropositivity (titer ⩾ 1:8) for poliovirus type 1 and 3. Results OPV0 did not affect the overall seropositivity at 6 weeks or 6 months of age for either polio 1 or 3. In 6-week-old infants, not receiving OPV0 was associated with significantly lower GMT for polio 1 and 3 (GMT ratio = 0.52 (95% CI = 0.33–0.79) for polio 1; 0.44 (0.28–0.70) for polio 3), the effect being significant in its own right in boys and in children whose mothers had low antibody levels. In contrast, in 6-month-old infants, not receiving OPV0 was associated with significantly higher GMT for polio 1 (GMT ratio = 2.10 (1.32–3.35)). This was significant in its own right in boys and in children of mothers with high antibody levels. Conclusions OPV0 may contribute to early polio protection, particularly in children of mothers with low antibody levels. However, OPV0 did not contribute to overall polio immunity after subsequent doses of OPV were given, and was associated with significantly lower antibody titers in children of mothers with high antibody levels. However, it did not negatively affect the proportion of seropositive children.
    Full-text · Article · Dec 2014 · Trials in Vaccinology
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    • ". VITA II randomized low birth weight neonates (<2500 g) 1:1 to 25,000 IU vitamin A or placebo (2005–2008) [2]. VITA III randomized normal birth weight neonates 1:1:1 to 50,000 IU vitamin A, 25,000 IU vitamin A or placebo (2004–2007) [3]. "
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    ABSTRACT: In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.5 months or no early MV, in addition to the usual MV at 9 months. We have previously found interactions between vitamin A and vaccines. OBJECTIVE We investigated whether there were interactions between NVAS and early MV. DESIGN We compared the mortality of NVAS and placebo recipients: first, from 4.5 to 8 months for children randomized to early MV or no early MV; and second, from 9 to 17 months in children who had received two MV or one MV. Mortality rates (MR) were compared in Cox models producing mortality rate ratios (MRR). RESULTS A total of 5141 children were randomized to NVAS (N=3015) or placebo (N=2126) and were later randomized to early MV (N=1700) or no early MV (N=3441). Between 4.5 and 8 months, NVAS compared with placebo was associated with higher mortality in early MV recipients (MR=30 versus MR=0, p=0.01), but not in children who did not receive early MV (p for interaction between NVAS and early MV=0.03). From 9 to 17 months NVAS was not associated with mortality. Overall, from 4.5 to 17 months NVAS was associated with increased mortality in early MV recipients (Mortality rate ratio=5.39 (95% confidence interval: 1.62, 17.99)). CONCLUSIONS These observations indicate that NVAS may interact with vaccines given several months later. This may have implications for the planning of future child intervention programs.
    Full-text · Article · Sep 2014 · Vaccine
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    • "Assessment of different effects in different population strata is also relevant for targeted interventions, as the effects might be different across population subgroups even within a disadvantaged group. For example, nutrition interventions targeting poor populations may have different effects on boys and girls [6]. "
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    ABSTRACT: Background The deadline for achieving Millennium Development Goals 4 and 5 is approaching, but inequalities between disadvantaged and other populations is a significant barrier for progress towards achieving these goals. This systematic review aims to collect evidence about the differential effects of interventions on different sociodemographic groups in order to identify interventions that were effective in reducing maternal or child health inequalities. Methods We searched the PubMed, EMBASE and other relevant databases. The reference lists of included reviews were also screened to find more eligible studies. We included experimental or observational studies that assessed the effects of interventions on maternal and child health, but only studies that report quantitative inequality outcomes were finally included for analysis. Results 22 articles about the effectiveness of interventions on equity in maternal and child health were finally included. These studies covered five kinds of interventions: immunization campaigns, nutrition supplement programs, health care provision improvement interventions, demand side interventions, and mixed interventions. The outcome indicators covered all MDG 4 and three MDG 5 outcomes. None of the included studies looked at equity in maternal mortality, adolescent birth rate and unmet need for family planning. The included studies reported inequalities based on gender, income, education level or comprehensive socioeconomic status. Stronger or moderate evidence showed that all kinds of the included interventions may be more effective in improving maternal or child health for those from disadvantaged groups. Conclusion Studies about the effectiveness of interventions on equity in maternal or child health are limited. The limited evidence showed that the interventions that were effective in reducing inequity included the improvement of health care delivery by outreach methods, using human resources in local areas or provided at the community level nearest to residents and the provision of financial or knowledge support to demand side.
    Full-text · Article · Jun 2014 · BMC Public Health
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