Effectiveness of LNS and MNP Supplements to Prevent Malnutrition in Women and Their Children in Bangladesh

Study Overview
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Brief Summary
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The program effectiveness study aims to assess the effect of a lipid-based nutrition supplement (LNS) and micronutrient powder (MNP) provided in a programmatic context for improving maternal nutritional status during pregnancy and lactation (LNS only), and preventing malnutrition in infants and young children (LNS and MNP) in Bangladesh.

Detailed Description
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This study is a cluster-randomized controlled trial with four study arms, implemented within the context of the Community Health and Development Program (CHDP) run by the World Mission Prayer League, which also has a hospital in the area and is known as LAMB. Data collection is longitudinal, starting with the identification of women in early pregnancy who are eligible to enter the study, and continuing, with follow-up of the child, until 24 months post-partum. A final follow-up visit will occur when the child is 36 months old to update contact information; no outcomes data will be collected at that final visit. The investigators are evaluating the effect of providing LNS-PLW to mothers during pregnancy and lactation on maternal health and nutrition outcomes (including anthropometric and micronutrient status), morbidity and birth outcomes in comparison to mothers who receive iron-folic acid tablets during pregnancy and lactation. The investigators are also evaluating the effect of three different home-fortification approaches (arms a-c, below) on child health and nutrition outcomes including anthropometric status, micronutrient status, anemia, and motor and cognitive development, in comparison to a control arm not receiving a home fortification intervention. Additionally, the cost of implementation and delivery of the LNS-PLW, LNS-child or MNP interventions as part of the CHDP compared to standard CHDP program delivery will be documented. Willingness to pay (private demand) for LNS-PLW, LNS-child and MNP products by selected caregivers and male heads of households will be assessed at baseline and again at various points during the intervention period. A process evaluation of the LNS and MNP interventions, and of the services provided to the control group, within the CHDP will be conducted to: 1) Document and evaluate the processes needed for implementation of interventions that provide a nutrient supplement such as LNS or MNP in the context of the CHDP; and 2) Explain and interpret program effectiveness study results and identify important facilitators and barriers to success of the nutrition intervention, which can be used to improve the effectiveness of current CHDP programs and future similar programs that include the scaling-up of LNS or MNP. A post-intervention follow-up assessment for participants in the RDNS trial was added to the study protocol in November 2015. The intervention stopped when the study children turned 24 months old, and follow-up visits to update contact information were conducted when the children turned 36 months old. Thereafter, when the study children are between 40 and 52 months old, the follow-up assessment includes anthropometric and cognitive development assessments and collection of blood samples (finger prick, for measurement of hemoglobin) and buccal swab samples at the local clinics; for the mothers the follow-up includes anthropometric measurements, measurement of blood pressure and collection of fasting blood samples (finger prick). The follow-up also includes anthropometric measurements of the younger siblings, as well as a home visit to collect information on socioeconomic status, food security, hospitalizations of mother or child, developmental stimulation in the home, child food preferences and retrospective perceptions about the trial interventions. Follow-up outcomes: Maternal: Body mass index, skinfold thickness, mid-upper arm circumference, attained height. Hemoglobin, anemia, blood pressure, blood lipids, HbA1C. Index child: Height, HAZ, stunting, weight, WHZ, WAZ, wasting, skinfold thickness, MUAC, arm fat and muscle area. Verbal ability (language), non-verbal ability (visual spatial), executive function and pre-academic skills. Hemoglobin, anemia. Hospitalizations since 24 months of age. Preferences for sweet and fatty foods. Younger sibling: Height, HAZ, stunting, weight, WHZ, WAZ, wasting, MUAC.

Official Title
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Home-fortification Approaches for the Prevention of Malnutrition in Pregnant and Lactating Women and Their Children in Bangladesh: Program Effectiveness Study

Conditions
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Malnutrition

Intervention / Treatment
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* Dietary Supplement: LNS-PLW
* Dietary Supplement: LNS-Child
* Dietary Supplement: MNP
* Dietary Supplement: IFA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age ≤ 20 weeks Planning to remain in the study area during pregnancy and the following three years (i.e., a permanent resident of the study area) Exclusion Criteria: Pregnancy identified and registered in the CHDP program before the beginning of the enrollment.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Comprehensive<br>Comprehensive LNS: LNS-PLW provided daily to mothers during pregnancy and postpartum lactation (a total of at least 11 months, starting by 20 weeks gestation and ending at 6 months post-partum) and LNS developed for infants and young children (LNS-child) provided daily to their infants (beginning at 6 months of age for a period of 18 months i.e., from 6-24 months of age). | Dietary Supplement: LNS-PLW<br>* Dietary supplement: Lipid-based nutrient supplement Lipid-based nutrient supplement for pregnant and lactating women (LNS-PLW) Daily dose of LNS-PLW will be 20 g, packaged in one sachet<br>Dietary Supplement: LNS-Child<br>* Dietary supplement: Lipid-based nutrient supplement Lipid-based nutrient supplement for infants and young children (LNS-Child) Daily dose of LNS-Child will be 20 g, packaged in two 10 g sachets<br>|
| Experimental: Child-only LNS<br>Child-only LNS: Daily LNS-child supplementation of the child starting at 6 months of age and ending at 24 months of age (18 months total). Women will be provided with iron and folic acid (IFA) tablets during pregnancy and for 3 months postpartum. | Dietary Supplement: LNS-Child<br>* Dietary supplement: Lipid-based nutrient supplement Lipid-based nutrient supplement for infants and young children (LNS-Child) Daily dose of LNS-Child will be 20 g, packaged in two 10 g sachets<br>Dietary Supplement: IFA<br>* Dietary supplement: Iron and folic acid nutrient supplement Iron-folic acid tablets for pregnant and lactating women Daily dose of iron-folic acid supplement will be one tablet containing 60 mg iron and 400 mcg folic acid<br>|
| Experimental: Child-only MNP<br>Child-only MNP: Daily MNP supplementation of the child starting at 6 months of age and ending at 24 months of age (18 months total). Women will be provided with iron and folic acid (IFA) tablets during pregnancy and for 3 months postpartum. | Dietary Supplement: MNP<br>* Dietary supplement: Micronutrient powder Micronutrient powder for infants and young children (MNP) The MNP for children will be packaged in 1 g sachets, so that each day, the child will consume one sachet.<br>Dietary Supplement: IFA<br>* Dietary supplement: Iron and folic acid nutrient supplement Iron-folic acid tablets for pregnant and lactating women Daily dose of iron-folic acid supplement will be one tablet containing 60 mg iron and 400 mcg folic acid<br>|
| Active Comparator: Control: IFA<br>Control: No additional nutrient supplementation for the child will be provided through the study, but the regular nutrition education and visits provided by the program frontline staff will continue. Women will be provided with iron and folic acid (IFA) tablets during pregnancy and for 3 months postpartum. | Dietary Supplement: IFA<br>* Dietary supplement: Iron and folic acid nutrient supplement Iron-folic acid tablets for pregnant and lactating women Daily dose of iron-folic acid supplement will be one tablet containing 60 mg iron and 400 mcg folic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birth weight | Birth weight of the infants (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements). | 
| Birth length | Birth length of the infants (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements) | 
| Child linear growth status at 24 months | Linear growth (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maternal weight between baseline and 36 wk gestation | Gestational weight gain from enrollment (by 20 weeks of gestation) through 36 weeks of gestation (women who received LNS for pregnant and lactating women (LNS-PLW) vs. a comparison group who received the standard care, iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Between 12-20 and 36 weeks of gestation | 
| Pre-eclampsia | Prevalence of pre-eclampsia (women who received LNS-PLW vs. women who received iron and folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | 36 weeks of gestation | 
| Duration of gestation | Duration of gestation (women who received LNS-PLW vs. women who received iron and folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Day 0 | 
| Pre-term delivery | Prevalence of pre-term delivery (delivery at <37 gestational weeks) in the infants (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Day 0 | 
| Low birth weight | Prevalence of low birth weight (birth weight < 2500 g) in the infants (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements) | 
| Small for gestational age (SGA) | Prevalence of SGA (birth weight < 10th percentile) in the infants (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements) | 
| Newborn stunting | Prevalence of newborn stunting (length-for-age z-score <-2) in the infants (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements) | 
| BMI z score at birth | BMI z score at birth (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements) | 
| Head circumference (HC) at birth | Head circumference at birth of the infants (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements) | 
| Small head size at birth | Prevalence of small head size (HC-z-score <-2) at birth (women who received LNS-PLW vs. women who received iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | Within 48 hours (or back calculated from later measurements) | 
| Change in maternal weight between 42 d and 6 mo postpartum | Postpartum weight change from 42 days through 6 mo postpartum (women who received LNS for pregnant and lactating women (LNS-PLW) vs. a comparison group who received the standard care, iron-folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), for time of year when outcome was assessed | Between 42 d and 6 mo postpartum | 
| Change in maternal iodine status between baseline and 6 mo postpartum | Prevalence of iodine deficiency during lactation (women who received LNS-PLW vs. women who received iron and folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal iodine status, baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Between 10-20 weeks of gestation and 6 months postpartum | 
| Change in maternal iron status between baseline and 6 months postpartum | Prevalence of iron deficiency during lactation (women who received LNS-PLW vs. women who received iron and folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal iron status, baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Between 10-20 weeks of gestation and 6 months postpartum | 
| Change in maternal iron-deficiency anemia between baseline and 6 months postpartum | Prevalence of iron-deficiency anemia during lactation (women who received LNS-PLW vs. women who received iron and folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal iron status, baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Between 10-20 weeks of gestation and 6 months postpartum | 
| Change in maternal anemia between baseline and 6 months postpartum | Prevalence of anemia during lactation (women who received LNS-PLW vs. women who received iron and folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal anemia status, baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Between 10-20 weeks of gestation and 6 months postpartum | 
| Change in maternal vitamin A status between baseline and 6 months postpartum | Prevalence of vitamin A deficiency during lactation (women who received LNS-PLW vs. women who received iron and folic acid tablets). Pre-defined tests for interaction will be done for: baseline maternal vitamin A status, baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Between 10-20 weeks of gestation and 6 months postpartum | 
| Change in maternal depressive symptoms between baseline and 6 months postpartum | Prevalence of depression during lactation (women who received LNS-PLW vs. a comparison group). Pre-defined tests for interaction will be done for: baseline maternal depression status, baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment) and time of year when outcome was assessed. | Between 10-20 weeks of gestation and 6 months postpartum | 
| Child hemoglobin concentration at 18 months of age | Hemoglobin concentration (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 18 months | 
| Child iron status at 18 months of age | Prevalence of iron deficiency (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 18 months | 
| Child vitamin A status at 18 months of age | Prevalence of vitamin A deficiency (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 18 months | 
| Child anemia status at 18 months of age | Prevalence of anemia in children (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 18 months | 
| Child iron-deficiency anemia status at 18 months of age | Prevalence of iron-deficiency anemia in children (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 18 months | 
| Wasting at 24 months of age | Prevalence of wasting (weight-for-length z-score <-2) in children (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 24 months | 
| Head circumference at 24 months of age | Head circumference of children (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 24 months | 
| Stunting at 24 months of age | Prevalence of stunting (length-for-age z-score <-2) in children (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 24 months | 
| Child motor development at 24 months of age | Motor development of children (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 24 months | 
| Child cognitive development at 24 months of age | Cognitive development of children (the comprehensive LNS approach vs. the child-only LNS approach vs. child-only MNP) vis-à-vis one another and vis-à-vis the control group. Pre-defined tests for interaction will be done for: baseline maternal characteristics (age, height, BMI, education, primiparity, food insecurity, wealth and gestational age at enrollment), time of year when outcome was assessed and child sex. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malnutrition, stunting, LNS, micronutrient powder, hemoglobin