Date of Award

11-10-2009

Degree Type

Thesis

Degree Name

PhD in Health Sciences

First Advisor

Dr. Zulfiqar A. Bhutta

Second Advisor

Dr. Saeed Hamid

Third Advisor

Dr. Tasleem Akhtar

Department

Paediatrics and Child Health

Abstract

Transition from exclusive breast feeding to complementary feeding poses many challenges as the demand for nutrients necessary for optimum growth and development increases steadily. Malnutrition and micronutrient malnutrition can be inter-generational and affect pregnant mothers and consequently the baby may be born with deficient micronutrient stores, especially those of iron. This deficiency can be further exacerbated by sub-optimal practices of breast feeding. Globally, iron deficiency is the most common cause of anemia estimated to affect nearly 2 billion people especially preschool children. In Pakistan, 56 % of children under the age of five years are estimated to have iron deficiency anemia and 13 % are also severely malnourished. These deficiencies affect not only physical growth but also mental development with significant impact on immunity and increased burden of infections. It is uncertain what the most appropriate intervention strategy is and a wide range of options are mentioned including dietary diversification through nutrition education, provision of fortified foods, iron supplementation and home-based fortification of complementary foods with micronutdent powders such as Spdnkles. In an effort to understand the prevalence of under nutrition and develop effective interventions for improving growth and micronutrient status of infants receiving complementary foods, I undertook a prospective community-based randomized controlled efficacy trial in a representative urban population of Karachi. Infants and mothers were identified after birth and enrolled in the study to receive one of the interventions through community health workers at the age of six months. The enrolled infants were placed in three groups - defined as Nutr Education (NuR Edu), Oral iron supplementation (OIS) and Multiple micronutrient fortification (MMF). Nutrition education component was common to all the groups. Through nutritional education sessions held in the community, dietary diversification along with continuation of breast feeding was stressed to enhance the intake of diet, rich in iron, and other micronutrients. A cohort of 451 infants (177 in group Nutr Edu, 141 in group oiS and 133 in MMF) were followed for three months (till the end of treatments) for growth, micronutrient status, and morbidity rate and thereafter followed for another three months to evaluate anthropometdc parameters. This community based randomized efficacy trial demonstrated that MMF which also contained iron, significantly improved the iron status (as reflected by mean Hemoglobin and mean Ferdtin concentrations in the recipients) and prevented the observed development of iron deficiency among infants as compared to nutrition education alone. Mean Hemoglobin level improved significantly between the groups to 10.30 gm/dl (95% CI; 10.02, 10.58) in MMF vs. 9.87 gm/dl (95% CI; 9.61, 10.12) in the Nutr Edu at the end of trial. The MMF and oiS groups were not found to be significantly different from each other for most of the indicators followed. There was an overall improvement in rate of anemia at the end of treatment between the groups, achieving significant reduction in anemia [relative risk (RR) of 0.81 (95 % CI; 0.68, 0.97)] for MMF compared with nutrition education alone and RR of 0.84 (95 % CI; 0.71, 1.00) of OIS compared to Nutrition education alone. In contrast the rates of iron deficiency anemia improved (p=0.037) at the end of treatment between the groups, with a relative risk (RR) of anemia reduction of 0.57 (95 % CI; 0.34-0.96) for MMF alone and RR of 0.59 (95 % CI; 0.36-0.97) of OIS alone in comparison with Nutr Edu group. The improvement in weight gain over the period of trial was significantly greater in the MME group in comparison with Nub Edu and C)IS groups, when analyzed using the mixed model. Although there was no significant difference detected between the groups for change in rates for wasting, stunting and under weight, the mean monthly weight gain and mean monthly WAZ scores during the trial period and mean WAZ scores at nine months of age found significant for MMF in comparison to Nutr Edu group. The mean monthly weight gain increased by 300 gm in the group MMF as compared to 240 gm (P= 0.014) in the Nutr Edu group and the mean monthly WAZ scores improved significantly by 0. 12 in MMF as compared to 0.04 in Nutr Edu group. Mean z scores of -0.15 for WHZ was found significantly different at 9 months of age for MMF in comparison to scores of -0.70 for Nutr Edu. Combined (pooled) effect was analyzed by adding the data (oiS + MMF) of those who received the added supplementation of iron in any of the form the results of which showed that addition of micronutrient led to significant improvement in mean increment in weight (p = 0.02), mean weight for height z scores (p=0.00), mean hemoglobin (p=0.01) and ferritin (< 0.01) levels, rates of anemia (p=0.01) and iron deficiency anemia (p=001), at the completion of treatment.>< 0.01) levels, rates of anemia (p=0.01) and iron deficiency anemia (p=001), at the completion of treatment. In the clinical trials conducted to evaluate the bioavailability of iron (stable isotopes) in the presence of Khitchri and additional ascorbic acid, iron absorption improved (p=0.0022) in the presence of ascorbic acid at a ratio of 2:1 and it improved further (p< 0.0001) as the ratio>< 0.0001) as the ratio was increased to 4:1. There was no statistically significant difference (p=0.158) observed between the test meals consumed with or without human milk in presence of additional ascorbic acid. n this community based randomized clinical trial, the nutrition education package implemented alone was not able to improve hematological parameters including the micronutrient status nor did it have any effect on growth indicators. Improvement in rates of anemia and iron deficiency anemia was observed in both of the groups; MMF and OIS, as compared to the Nutr Edu group with greater improvement in growth observed in infants receiving MMF. Moreover the results showed significant improvement in iron absorption with higher dose of ascorbic acid (vitamin C). However, the addition of breast milk did not further enhance iron absorption from complementary food suggesting that this strategy alone could not be relied upon to improve iron absorption from weaning foods and that the addition of fruits and fruit juice with adequate vitamin C would be needed to enhance iron bioavailability. The findings of this study confirm that more than one micronutrient may be needed to improve nutrient intake, iron absorption, and growth in infancy and support the contention that appropriate complementary feeding strategies in poor populations with limited diet may need the combination of diverse foods with suitable micronutrient supplements.

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