Cost-effectiveness of prenatal food and micronutrient interventions on under-five mortality and stunting: Analysis of data from the MINIMat randomized trial, Bangladesh.

INTRODUCTION: Nutrition interventions may have favourable as well as unfavourable effects. The Maternal and Infant Nutrition Interventions in Matlab (MINIMat), with early prenatal food and micronutrient supplementation, reduced infant mortality and were reported to be very cost-effective. However, the multiple micronutrients (MMS) supplement was associated with an increased risk of stunted growth in infancy and early childhood. This unfavourable outcome was not included in the previous cost-effectiveness analysis. The aim of this study is to evaluate whether the MINIMat interventions remain cost-effective in view of both favourable (decreased under-five-years mortality) and unfavourable (increased stunting) outcomes. METHOD: Pregnant women in rural Bangladesh, where food insecurity still is prevalent, were randomized to early (E) or usual (U) invitation to be given food supplementation and daily doses of 30 mg, or 60 mg iron with 400 µg of folic acid, or MMS with 15 micronutrients including 30 mg iron and 400 µg of folic acid. E reduced stunting at 4.5 years compared with U, MMS increased stunting at 4.5 years compared with Fe60, while the combination EMMS reduced infant mortality compared with UFe60. The outcome measure used was disability adjusted life years (DALYs), a measure of overall disease burden that combines years of life lost due to premature mortality (under five-year mortality) and years lived with disability (stunting). Incremental cost effectiveness ratios were calculated using cost data from already published studies. RESULTS: By incrementing UFe60 (standard practice) to EMMS, one DALY could be averted at a cost of US$24. CONCLUSION: When both favourable and unfavourable outcomes were included in the analysis, early prenatal food and multiple micronutrient interventions remained highly cost effective and seem to be meaningful from a public health perspective.

Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity.

AIM: A previous maternal and infant nutrition intervention in rural Matlab, Bangladesh, showed that prenatal nutrient supplements improved child survival, but had no effect on size at birth. This secondary analysis examined whether prenatal multiple micronutrient supplements (MMS), on their own or combined with an early invitation to receive prenatal food supplements, affected child morbidity. METHODS: This randomised trial enrolled 4436 pregnant women from November 2001 to October 2003 and allocated them to early or standard invitations to food supplements, in the ninth and 20th weeks of pregnancy, respectively, and supplements of either the standard 60 mg iron with 400 µg folic acid, 30 mg iron with 400 µg folic acid or MMS. Quasi-Poisson regression was used to analyse morbidity. RESULTS: There were 3560 single live births and 3516 had morbidity data. The incidence rates of fever, diarrhoea and acute lower respiratory tract infection were 15.3, 3.6 and 2.3 episodes per person-year, respectively. The separate or combined interventions had no effect on morbidity up to 24 months. CONCLUSION: Early invitations to prenatal food supplements or prenatal MMS had no effect on common infections in rural Bangladesh, suggesting that earlier findings on improved child survival were not mediated by an effect on child morbidity.

Effects of prenatal micronutrient and early food supplementation on metabolic status of the offspring at 4.5 years of age. The MINIMat randomized trial in rural Bangladesh.

BACKGROUND: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype. METHODS: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 µg of folic acid, 60 mg of iron and 400 µg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress. RESULTS: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 µg folic acid. There were no effects on markers of inflammation or oxidative stress. CONCLUSIONS: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.

Integrated paediatric fever management and antibiotic over-treatment in Malawi health facilities: data mining a national facility census.

BACKGROUND: There are growing concerns about irrational antibiotic prescription practices in the era of test-based malaria case management. This study assessed integrated paediatric fever management using malaria rapid diagnostic tests (RDT) and Integrated Management of Childhood Illness (IMCI) guidelines, including the relationship between RDT-negative results and antibiotic over-treatment in Malawi health facilities in 2013-2014. METHODS: A Malawi national facility census included 1981 observed sick children aged 2-59 months with fever complaints. Weighted frequencies were tabulated for other complaints, assessments and prescriptions for RDT-confirmed malaria, IMCI-classified non-severe pneumonia, and clinical diarrhoea. Classification trees using model-based recursive partitioning estimated the association between RDT results and antibiotic over-treatment and learned the influence of 38 other input variables at patient-, provider- and facility-levels. RESULTS: Among 1981 clients, 72 % were tested or referred for malaria diagnosis and 85 % with RDT-confirmed malaria were prescribed first-line anti-malarials. Twenty-eight percent with IMCI-pneumonia were not prescribed antibiotics (under-treatment) and 59 % 'without antibiotic need' were prescribed antibiotics (over-treatment). Few clients had respiratory rates counted to identify antibiotic need for IMCI-pneumonia (18 %). RDT-negative children had 16.8 (95 % CI 8.6-32.7) times higher antibiotic over-treatment odds compared to RDT-positive cases conditioned by cough or difficult breathing complaints. CONCLUSIONS: Integrated paediatric fever management was sub-optimal for completed assessments and antibiotic targeting despite common compliance to malaria treatment guidelines. RDT-negative results were strongly associated with antibiotic over-treatment conditioned by cough or difficult breathing complaints. A shift from malaria-focused 'test and treat' strategies toward 'IMCI with testing' is needed to improve quality fever care and rational use of both anti-malarials and antibiotics in line with recent global commitments to combat resistance.