The effect of vitamin D supplementation on the glycemic control of pre-diabetic Qatari patients in a randomized control trial.

BACKGROUND: Vitamin D deficiency is associated with indicators of pre-diabetes including, insulin resistance, ß-cell dysfunction and elevated plasma glucose with controversial findings from current trials. This study aims to investigate the long-term effect of vitamin D on glucose metabolism and insulin sensitivity in pre-diabetic and highly vitamin-deficient subjects. METHODS: One hundred thirty-two participants were randomized to 30,000 IU vitamin D weekly for 6 months. Participants underwent oral glucose tolerance test (OGTT) at 3-month intervals to determine the change in plasma glucose concentration at 2 h after 75 g OGTT (2hPCG). Secondary measurements included glycated hemoglobin, fasting plasma glucose and insulin, post-prandial insulin, indices of insulin sensitivity (HOMA-IR, Matsuda Index), ß-cell function (HOMA-ß, glucose and insulin area under the curve (AUC), disposition and insulinogenic indices), and lipid profile. RESULTS: A total of 57 (vitamin D) and 75 (placebo) subjects completed the study. Mean baseline serum 25(OH) D levels were 17.0 ng/ml and 14.9 ng/ml for placebo and vitamin D group, respectively. No significant differences were observed for 2hPC glucose or insulin sensitivity indices between groups. HOMA-ß significantly decreased in the vitamin D group, while area under curve for glucose and insulin showed a significant reduction in ß-cell function in both groups. Additionally, HOMA-ß was found to be significantly different between control and treatment group and significance persisted after adjusting for confounding factors. CONCLUSION: Vitamin D supplementation in a pre-diabetic and severely vitamin-deficient population had no effect on glucose tolerance or insulin sensitivity. The observed reduction in ß-cell function in both placebo and vitamin D groups could be attributed to factors other than supplementation. TRIAL REGISTRATION: NCT02098980, 28/03/2014 (www.clinicaltrials.gov).

Reducing micronutrient deficiencies in Pakistani children: are subsidies on fortified complementary foods cost-effective?

OBJECTIVE: To estimate the cost-effectiveness of price subsidies on fortified packaged complementary foods (FPCF) in reducing iodine deficiency, iron-deficiency anaemia and vitamin A deficiency in Pakistani children. DESIGN: The study proceeded in three steps: (i) we determined the current lifetime costs of the three micronutrient deficiencies with a health economic model; (ii) we assessed the price sensitivity of demand for FPCF with a market survey in two Pakistani districts; (iii) we combined the findings of the first two steps with the results of a systematic review on the effectiveness of FPCF in reducing micronutrient deficiencies. The cost-effectiveness was estimated by comparing the net social cost of price subsidies with the disability-adjusted life years (DALY) averted. SETTING: Districts of Faisalabad and Hyderabad in Pakistan. SUBJECTS: Households with 6-23-month-old children stratified by socio-economic strata. RESULTS: The lifetime social costs of iodine deficiency, iron-deficiency anaemia and vitamin A deficiency in 6-23-month-old children amounted to production losses of $US 209 million and 175 000 DALY. Poor households incurred the highest costs, yet even wealthier households suffered substantial losses. Wealthier households were more likely to buy FPCF. The net cost per DALY of the interventions ranged from a return per DALY averted of $US 783 to $US 65. Interventions targeted at poorer households were most cost-effective. CONCLUSIONS: Price subsidies on FPCF might be a cost-effective way to reduce the societal costs of micronutrient deficiencies in 6-23-month-old children in Pakistan. Interventions targeting poorer households are especially cost-effective.

Effect of provision of home-based curative health services by public sector health-care providers on neonatal survival: a community-based cluster-randomised trial in rural Pakistan.

BACKGROUND: Although the effectiveness of community mobilisation and promotive care delivered by community health workers in reducing perinatal and neonatal mortality is well established, evidence in support of home-based neonatal resuscitation and infection management is mixed. We assessed the effectiveness of adding training in neonatal bag and mask resuscitation and oral antibiotic therapy for suspected neonatal infections to a basic preventive and promotive interventions package delivered by public sector community-based lady health workers (LHWs) in rural Pakistan. METHODS: We did a cluster-randomised controlled trial in two subdistricts of Naushahro Feroze in rural Sindh, Pakistan, between April 15, 2009, and Dec 10, 2012. LHWs, trained in basic newborn resuscitation and in recognition and treatment (with oral amoxicillin) of suspected neonatal respiratory infections, were linked with traditional birth attendants and encouraged to attend home births. Control clusters received routine care through the existing national programme. The primary outcome was all-cause neonatal mortality. Independent data collection teams recorded data for all pregnancies and their outcomes, morbidity, mortality, and household practices related to maternal and newborn care. FINDINGS: Of the 27 randomised clusters with functional LHW programmes, 13 were allocated to the intervention group (n=242 749) and 14 to the control group (n=256 985). In the intervention group, LHWs did 80% of the planned community mobilisation sessions, but were able to attend only 1184 (14%) of 8425 deliveries and 4318 (25%) of 17 288 neonatal visits within 72 h of birth (p<0·0001 for both variables compared with the control group). The neonatal mortality rate was 42 deaths per 1000 livebirths in intervention clusters compared with 55 per 1000 in the control group (risk ratio 0·80, 95% CI 0·68-0·93; p=0·005). INTERPRETATION: The reduction in neonatal mortality in intervention clusters occurred against a background of improvements in domiciliary practices for maternal and newborn care. However, the poor reach of LHWs in accessing newborn infants at birth and in the early postnatal period underscores the limitations of tasking community health workers in public sector programmes working in similar circumstances with such complex interventions. Such community-based interventions in health systems should be accompanied by concerted efforts to improve quality of care in facilities and referral systems. FUNDING: Saving Newborn Lives, Save the Children USA.

Evaluation of the uptake and impact of neonatal vitamin A supplementation delivered through the Lady Health Worker programme on neonatal and infant morbidity and mortality in rural Pakistan: an effectiveness trial.

BACKGROUND: Despite evidence for the benefits of vitamin A supplementation (VAS) among children 6 to 59 months of age, the feasibility of introduction and potential benefit of VAS in the neonatal period in public health programmes is uncertain. OBJECTIVE: The primary objective was to evaluate the feasibility and effectiveness of early neonatal VAS (single dose of 50 000 international units within 48-72 hours after birth) delivered through the public sector Lady Health Worker (LHW) programme in rural Pakistan and to document its association with a reduction in mortality at 6 months of age. METHODS: A community-based, cluster randomised, placebo-controlled trial was undertaken in two districts of rural Pakistan. LHWs dispensed vitamin A/placebo in identical capsules to newborn infants within 48-72 hours of birth. Follow-up visits were undertaken at 1 week of age and every 4 weeks thereafter until 6 months of age. RESULTS: Of a total of 15 433 consecutive pregnancies among eligible women of reproductive age, 13 225 pregnancies were registered, 12 218 live births identified and 11 028 newborn infants reached by LHWs. Of these, 5380 (49%) received neonatal VAS and 5648 (51%) placebo. The LHWs successfully delivered the capsules to 79% of newborns within 72 hours of birth with no significant adverse effects. Although the proportion of days observed with symptoms of fever, diarrhoea or rapid breathing were lower with neonatal VAS, these differences were not statistically significant. Mortality rates in the two groups were comparable at 6 months of age. CONCLUSIONS: While our study demonstrated that neonatal VAS was safe and could be feasibly delivered by LHWs in Pakistan as part of their early postnatal visits, the overall lack of benefit on neonatal and 6-month morbidity and mortality in our population suggests the need for further evaluation of this intervention in populations at risk. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00674089.

Prevalence and Predictors of Iron Deficiency Anemia in Children under Five Years of Age in Pakistan, A Secondary Analysis of National Nutrition Survey Data 2011-2012.

BACKGROUND: Iron deficiency Anemia (IDA) in children is a recognized public health problem that impacts adversely on child morbidity, mortality and impairs cognitive development. In Pakistan information on the true prevalence and predictors of IDA is limited. This study sought to investigate IDA in children under five years of age using data from a nationally representative stratified cross-sectional survey. METHODS: Secondary analysis was performed on the National Nutrition Survey in Pakistan 2011-2012. We used a pre-structured instrument to collect socio demographic and nutritional data on mothers and children. We also collected Anthropometric measurements and blood samples for micronutrient deficiencies. IDA was defined as having both haemoglobin levels of <110 g/L and ferritin levels of < 12 µg/L. Data analysis was performed by applying univariate and multivariate techniques using logistic regression through SPSS. FINDINGS: A total of 7138 children aged between 6-59 months were included in the analysis. The prevalence of IDA was 33.2%. In multivariate regression analysis adjusted odds ratios (AOR) were calculated. Age < 24 months (AOR 1.40, 95% CI 1.18-1.55 p <0.05), stunting (AOR 1.42 CI 1.23-1.63 p<0.05), presence of clinical anemia (AOR 5.69 CI 4.93-6.56 p<0.05), having a mother with IDA (AOR 1.72 CI 1.47-2.01 p<0.05) and household food insecurity (AOR 1.20 CI 1.10-1.40 P<0.05) were associated with IDA. Living in a rural area (AOR 0.77 CI 0.65-0.90 p<0.05) and being a female child (AOR 0.87 CI 0.76-0.98 p<0.05) were associated with reduced odds of IDA. CONCLUSION: The prevalence of IDA amongst Pakistani children represents a moderate burden that disproportionately affects the youngest, growth retarded children, affected children are more likely to have mothers with IDA and live in areas where food security is lacking. National efforts to alleviate the burden of IDA should involve both short term vertical programs such as iron supplementation and long term horizontal programs including wheat flour fortification.

Absorbed zinc and exchangeable zinc pool size are greater in Pakistani infants receiving traditional complementary foods with zinc-fortified micronutrient powder.

Adequacy of zinc intake from breast milk alone becomes marginal in relation to infant requirements by around 6 mo of age. Simple and cost-effective strategies are needed at the population level to ensure adequate intakes of zinc in infants and toddlers in populations at risk of zinc deficiency. We determined the amount of absorbed zinc (AZ) from a micronutrient powder (MNP) without and with 10 mg of zinc (MNP+Zn) added to local complementary foods used in Pakistan and the impact on the exchangeable zinc pool (EZP) size. As a nested study within a large, prospective, cluster randomized trial, 6-mo-old infants were randomly assigned to receive MNP or MNP+Zn. Stable isotope methodology was applied after ∼3 and 9 mo of use to measure AZ from MNP-fortified test meals of rice-lentils (khitchri) and EZP. Nineteen infants per group completed the first metabolic studies and 14 and 17 infants in the MNP and MNP+Zn groups, respectively, completed the follow-up studies. AZs were (mean ± SD) 0.1 ± 0.1 and 1.2 ± 0.5 mg at the first point for the MNP and MNP+Zn groups, respectively (P < 0.001); results were nearly identical at the follow-up measurement. EZP did not differ between groups at the first measurement but was less in the MNP group (3.7 ± 0.6 mg/kg) than in the MNP+Zn group (4.5 ± 1.0 mg/kg) at the second measurement (P = 0.01). These data confirm that the MNP+Zn in khitchri were well absorbed and after 1 y of home fortification, zinc status assessed by EZP was significantly better for the MNP+Zn group. Additional field studies may be necessary to ascertain the adequacy of this dose for infants at high risk of deficiency. This trial was registered at ClinicalTrials.gov as NCT00705445.