<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01665378</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00051384</org_study_id>
    <secondary_id>10-1196-UEMORY-01</secondary_id>
    <nct_id>NCT01665378</nct_id>
  </id_info>
  <brief_title>Impact of Pre-pregnancy Micronutrient Supplementation on Maternal and Child Outcomes</brief_title>
  <official_title>Impact of Pre-Pregnancy Micronutrient Supplementation on Maternal and Child Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Micronutrient Initiative</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Mathile Institute for the Advancement of Human Nutrition</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study evaluates the efficacy of providing weekly iron-folate (IFA) supplements or&#xD;
      Multiple Micronutrient (MM) supplements before pregnancy in increasing birth weight and&#xD;
      duration of gestation as well as maternal and infant iron status.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Low birth weight and anemia remain intractable problems in many developing countries despite&#xD;
      considerable efforts to address them. Intervening with just prenatal iron-folate (IFA)&#xD;
      supplements may not be the best approach given the substantial demands for iron by maternal&#xD;
      and fetal tissues. Therefore, there is an urgent need to evaluate the additional contribution&#xD;
      of prepregnancy interventions.&#xD;
&#xD;
      The study evaluates the efficacy of providing weekly iron-folate (IFA) supplements or&#xD;
      Multiple Micronutrient (MM) supplements before pregnancy in increasing birth weight and&#xD;
      duration of gestation as well as maternal and infant iron status.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2011</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Birth Size</measure>
    <time_frame>At birth</time_frame>
    <description>Infants' weight, length and head circumference will be measured as early as possible within 24 hours after birth using standard procedures. All measurements will be obtained in duplicate by the same data collector. Weight-for-age and length-for-age z scores will be calculated using the 2006 WHO reference data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gestational Age</measure>
    <time_frame>At birth</time_frame>
    <description>Gestational age will be calculated based on the date of last menstrual period. This method has been shown to be reliable in previous work and we expect precise estimates since we will be visiting women weekly from baseline during the prepregnancy period and will exclude women who may be have delivered in the past 6 months.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Child growth</measure>
    <time_frame>From birth through 24 months</time_frame>
    <description>Length and weight will be measured at birth, 1, 3, 6, 9, 12, 15, 18, and 24 mo</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Child development</measure>
    <time_frame>Up to 7 years post enrollment</time_frame>
    <description>Child development will be measured using the Bayley Scales for Infant Development III at 12 and 24 mo and the Wechsler Intelligence Scale for Children at age 6-7 y</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Weight-for-age Z score (WAZ)</measure>
    <time_frame>Up to 7 years post enrollment</time_frame>
    <description>Weight-for-age Z score (WAZ) in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Height-for-age Z score (HAZ)</measure>
    <time_frame>Up to 7 years post enrollment</time_frame>
    <description>Height-for-age Z score (HAZ) in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Weight -for-Height Z (WHZ) or Body Mass Index Z score (BMIZ)</measure>
    <time_frame>Up to 7 years post enrollment</time_frame>
    <description>Weight -for-Height Z score (WHZ) or BMIZ in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Body composition (Lean mass/fat free mass index)</measure>
    <time_frame>Up to 7 years post enrollment</time_frame>
    <description>Body composition (Lean mass/fat free mass index) in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mothers' iron status</measure>
    <time_frame>At baseline and 1 and 3 months post partum</time_frame>
    <description>Venous blood samples (5 ml) will be collected from women at: baseline, the first prenatal visit and at 1 and 3 months post partum. Anemia will be defined as Hb value &lt;12 g/L for non-pregnant women,and &lt;11g/L for pregnant women and infants, and iron deficiency as serum ferritin &lt;12 μg/L (93).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants' iron status</measure>
    <time_frame>1 and 3 months of age</time_frame>
    <description>Infant iron status will be measured in cord blood samples (5 ml) obtained at delivery and at 3 months of age using a capillary blood sample (100 l) that will be obtained from a heel prick.&#xD;
The hemoglobin concentration will be measured from a drop of blood using the HEMOCUE B- Hb photometer. The blood samples will then be centrifuged and serum samples will be aliquotted into microcuvettes and handled in the same way as described for mothers. Serum ferritin and transferrin receptor concentrations will be assayed using the ELISA method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal depression</measure>
    <time_frame>At baseline, during pregnancy, 3 months postpartum</time_frame>
    <description>Center for Epidemiological Studies Depression Scale (CES-D) and Edinburgh Postnatal Depression Scale (EPDS)</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">5011</enrollment>
  <condition>Anemia</condition>
  <condition>Intrauterine Growth Retardation</condition>
  <condition>Preterm Delivery</condition>
  <condition>Iron Deficiency</condition>
  <arm_group>
    <arm_group_label>Multiple micronutrient - 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Multiple micronutrient groups 1 and 2 receive:&#xD;
Vitamin A (μg) 800 Vitamin D (IU) 600 Vitamin E (mg) 10 Vitamin C (mg) 70 Thiamine (mg) 1.4 Riboflavin (mg) 1.4 Niacin (mg) 18 Vitamin B6 (mg) 1.9 Vitamin B12 (μg) 2.6 Folic acid (μg)* 2800 Iron (mg)* 60 Zinc (mg) 15 Copper (mg) 2 Selenium (μg) 65 Iodine (μg) 150</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Iron and folic acid - 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Iron and folic acid groups 1 and 2 receive: iron (60mg) and folic acid (2800μg), based on current WHO recommendations for WRA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Folic Acid - 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Folic acid groups 1 and 2 receive: 2800 μg FA once a week during the pre-pregnancy period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Micronutrient - 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Multiple micronutrient groups 1 and 2 receive:&#xD;
Vitamin A (μg) 800 Vitamin D (IU) 600 Vitamin E (mg) 10 Vitamin C (mg) 70 Thiamine (mg) 1.4 Riboflavin (mg) 1.4 Niacin (mg) 18 Vitamin B6 (mg) 1.9 Vitamin B12 (μg) 2.6 Folic acid (μg)* 2800 Iron (mg)* 60 Zinc (mg) 15 Copper (mg) 2 Selenium (μg) 65 Iodine (μg) 150</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Iron and Folic Acid - 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Iron and folic acid groups 1 and 2 receive: iron (60mg) and folic acid (2800μg), based on current WHO recommendations for WRA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Folic acid - 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Folic acid groups 1 and 2 receive: 2800 μg FA once a week during the pre-pregnancy period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Multiple Micronutrient</intervention_name>
    <description>There is no current recommendation for weekly MM supplements for WRA. Therefore, we propose a supplement that contains: The same amounts of iron and folic acid as the weekly, pre-natal IFA supplement; An amount of vitamin D based on the Food and Nutrition Board's Recommended Daily Allowances (RDA); UNICEF/WHO/UNU recommended amounts of remaining nutrients (UNIMMAP recommendations). The supplement is taken weekly during pre-pregnancy.&#xD;
Vitamin A (μg) 800 Vitamin D (IU) 600 Vitamin E (mg) 10 Vitamin C (mg) 70 Thiamine (mg) 1.4 Riboflavin (mg) 1.4 Niacin (mg) 18 Vitamin B6 (mg) 1.9 Vitamin B12 (μg) 2.6 Folic acid (μg)* 2800 Iron (mg)* 60 Zinc (mg) 15 Copper (mg) 2 Selenium (μg) 65 Iodine (μg) 150</description>
    <arm_group_label>Multiple Micronutrient - 2</arm_group_label>
    <arm_group_label>Multiple micronutrient - 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Iron and Folic Acid</intervention_name>
    <description>The doses of weekly and daily iron (60mg) and folic acid (2800μg) are based on current WHO recommendations for WRA.</description>
    <arm_group_label>Iron and Folic Acid - 2</arm_group_label>
    <arm_group_label>Iron and folic acid - 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Folic Acid</intervention_name>
    <description>It is unethical to have a placebo group as FA is universally recommended for WRA to prevent neural tube defects. Therefore, the control group will receive 2800 μg FA once a week during the pre-pregnancy period. This dosage is safe and meets the minimum recommended intake of 400 μg/d for Women of Reproductive Age (WRA). Recent studies have shown that a weekly dose of 2800 μg FA is as effective as a daily dose of 400 μg in improving folic acid and reducing homocysteine levels among WRA.</description>
    <arm_group_label>Folic Acid - 1</arm_group_label>
    <arm_group_label>Folic acid - 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-35 years old&#xD;
&#xD;
          -  Currently married&#xD;
&#xD;
          -  Currently living in one of the 10 communes and intends to live in the areas for 24&#xD;
             months following recruitment&#xD;
&#xD;
          -  Plans to have children in the next year&#xD;
&#xD;
          -  Agrees to participate with informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently pregnant&#xD;
&#xD;
          -  Delivered in the previous six months&#xD;
&#xD;
          -  Regularly consumed IFA or MM supplements in the past 2 months&#xD;
&#xD;
          -  Severe anemia (Hb &lt; 7 g/L)&#xD;
&#xD;
          -  History of high risk pregnancy including abruptio placenta, placenta previa,&#xD;
             gestational diabetes, pregnancy induced hypertension, coagulation disorders,&#xD;
             thrombocytopenia or chronic vascular, renal or systemic disease and drug use&#xD;
&#xD;
          -  Chronic hematological diseases, hereditary defects of red cells or hemoglobin&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Usha Ramakrishnan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Thainguyen University of Medicine and Pharmacy</name>
      <address>
        <city>Hành Phố Thái Nguyên</city>
        <state>Thái Nguyên</state>
        <zip>24000</zip>
        <country>Vietnam</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Vietnam</country>
  </location_countries>
  <reference>
    <citation>Nguyen PH, Lowe AE, Martorell R, Nguyen H, Pham H, Nguyen S, Harding KB, Neufeld LM, Reinhart GA, Ramakrishnan U. Rationale, design, methodology and sample characteristics for the Vietnam pre-conceptual micronutrient supplementation trial (PRECONCEPT): a randomized controlled study. BMC Public Health. 2012 Oct 24;12:898. doi: 10.1186/1471-2458-12-898.</citation>
    <PMID>23092451</PMID>
  </reference>
  <reference>
    <citation>Nguyen PH, Gonzalez-Casanova I, Young MF, Truong TV, Hoang H, Nguyen H, Nguyen S, DiGirolamo AM, Martorell R, Ramakrishnan U. Preconception Micronutrient Supplementation with Iron and Folic Acid Compared with Folic Acid Alone Affects Linear Growth and Fine Motor Development at 2 Years of Age: A Randomized Controlled Trial in Vietnam. J Nutr. 2017 Aug;147(8):1593-1601. doi: 10.3945/jn.117.250597. Epub 2017 Jun 14.</citation>
    <PMID>28615372</PMID>
  </reference>
  <results_reference>
    <citation>Nguyen PH, DiGirolamo AM, Gonzalez-Casanova I, Pham H, Hao W, Nguyen H, Truong TV, Nguyen S, Harding KB, Reinhart GA, Martorell R, Ramakrishnan U. Impact of preconceptional micronutrient supplementation on maternal mental health during pregnancy and postpartum: results from a randomized controlled trial in Vietnam. BMC Womens Health. 2017 Jun 17;17(1):44. doi: 10.1186/s12905-017-0401-3.</citation>
    <PMID>28623904</PMID>
  </results_reference>
  <results_reference>
    <citation>Nguyen PH, Young M, Gonzalez-Casanova I, Pham HQ, Nguyen H, Truong TV, Nguyen SV, Harding KB, Reinhart GA, Martorell R, Ramakrishnan U. Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam. PLoS One. 2016 Dec 5;11(12):e0167416. doi: 10.1371/journal.pone.0167416. eCollection 2016.</citation>
    <PMID>27918586</PMID>
  </results_reference>
  <results_reference>
    <citation>Ramakrishnan U, Nguyen PH, Gonzalez-Casanova I, Pham H, Hao W, Nguyen H, Truong TV, Nguyen S, Harding KB, Reinhart GA, Neufeld LM, Martorell R. Neither Preconceptional Weekly Multiple Micronutrient nor Iron-Folic Acid Supplements Affect Birth Size and Gestational Age Compared with a Folic Acid Supplement Alone in Rural Vietnamese Women: A Randomized Controlled Trial. J Nutr. 2016 Jul;146(7):1445S-52S. doi: 10.3945/jn.115.223420. Epub 2016 Jun 8.</citation>
    <PMID>27281806</PMID>
  </results_reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2012</study_first_posted>
  <last_update_submitted>July 7, 2021</last_update_submitted>
  <last_update_submitted_qc>July 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Usha Ramakrishnan</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>prepregnancy</keyword>
  <keyword>micronutrient</keyword>
  <keyword>supplementation</keyword>
  <keyword>maternal</keyword>
  <keyword>child</keyword>
  <keyword>health</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Fetal Growth Retardation</mesh_term>
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folic Acid</mesh_term>
    <mesh_term>Vitamin B Complex</mesh_term>
    <mesh_term>Micronutrients</mesh_term>
    <mesh_term>Trace Elements</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01665378
org study id: IRB00051384
secondary id: 10-1196-UEMORY-01
nct id: NCT01665378
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The study evaluates the efficacy of providing weekly iron-folate (IFA) supplements or
      Multiple Micronutrient (MM) supplements before pregnancy in increasing birth weight and
      duration of gestation as well as maternal and infant iron status.
Low birth weight and anemia remain intractable problems in many developing countries despite
      considerable efforts to address them. Intervening with just prenatal iron-folate (IFA)
      supplements may not be the best approach given the substantial demands for iron by maternal
      and fetal tissues. Therefore, there is an urgent need to evaluate the additional contribution
      of prepregnancy interventions.

      The study evaluates the efficacy of providing weekly iron-folate (IFA) supplements or
      Multiple Micronutrient (MM) supplements before pregnancy in increasing birth weight and
      duration of gestation as well as maternal and infant iron status.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Birth Size
time frame: At birth
description: Infants' weight, length and head circumference will be measured as early as possible within 24 hours after birth using standard procedures. All measurements will be obtained in duplicate by the same data collector. Weight-for-age and length-for-age z scores will be calculated using the 2006 WHO reference data.
measure: Gestational Age
time frame: At birth
description: Gestational age will be calculated based on the date of last menstrual period. This method has been shown to be reliable in previous work and we expect precise estimates since we will be visiting women weekly from baseline during the prepregnancy period and will exclude women who may be have delivered in the past 6 months.
measure: Child growth
time frame: From birth through 24 months
description: Length and weight will be measured at birth, 1, 3, 6, 9, 12, 15, 18, and 24 mo
measure: Child development
time frame: Up to 7 years post enrollment
description: Child development will be measured using the Bayley Scales for Infant Development III at 12 and 24 mo and the Wechsler Intelligence Scale for Children at age 6-7 y
measure: Weight-for-age Z score (WAZ)
time frame: Up to 7 years post enrollment
description: Weight-for-age Z score (WAZ) in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements
measure: Height-for-age Z score (HAZ)
time frame: Up to 7 years post enrollment
description: Height-for-age Z score (HAZ) in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements
measure: Weight -for-Height Z (WHZ) or Body Mass Index Z score (BMIZ)
time frame: Up to 7 years post enrollment
description: Weight -for-Height Z score (WHZ) or BMIZ in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements
measure: Body composition (Lean mass/fat free mass index)
time frame: Up to 7 years post enrollment
description: Body composition (Lean mass/fat free mass index) in offspring of women receiving only FA, offspring of women who receive weekly pre-pregnancy IFA, and offspring of women who receive weekly MM supplements
measure: Mothers' iron status
time frame: At baseline and 1 and 3 months post partum
description: Venous blood samples (5 ml) will be collected from women at: baseline, the first prenatal visit and at 1 and 3 months post partum. Anemia will be defined as Hb value <12 g/L for non-pregnant women,and <11g/L for pregnant women and infants, and iron deficiency as serum ferritin <12 μg/L (93).
measure: Infants' iron status
time frame: 1 and 3 months of age
description: Infant iron status will be measured in cord blood samples (5 ml) obtained at delivery and at 3 months of age using a capillary blood sample (100 l) that will be obtained from a heel prick.
The hemoglobin concentration will be measured from a drop of blood using the HEMOCUE B- Hb photometer. The blood samples will then be centrifuged and serum samples will be aliquotted into microcuvettes and handled in the same way as described for mothers. Serum ferritin and transferrin receptor concentrations will be assayed using the ELISA method.
measure: Maternal depression
time frame: At baseline, during pregnancy, 3 months postpartum
description: Center for Epidemiological Studies Depression Scale (CES-D) and Edinburgh Postnatal Depression Scale (EPDS)
arm group label: Multiple micronutrient - 1
arm group type: Experimental
description: The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Multiple micronutrient groups 1 and 2 receive:
Vitamin A (μg) 800 Vitamin D (IU) 600 Vitamin E (mg) 10 Vitamin C (mg) 70 Thiamine (mg) 1.4 Riboflavin (mg) 1.4 Niacin (mg) 18 Vitamin B6 (mg) 1.9 Vitamin B12 (μg) 2.6 Folic acid (μg)* 2800 Iron (mg)* 60 Zinc (mg) 15 Copper (mg) 2 Selenium (μg) 65 Iodine (μg) 150
arm group label: Iron and folic acid - 1
arm group type: Active Comparator
description: The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Iron and folic acid groups 1 and 2 receive: iron (60mg) and folic acid (2800μg), based on current WHO recommendations for WRA.
arm group label: Folic Acid - 1
arm group type: Placebo Comparator
description: The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Folic acid groups 1 and 2 receive: 2800 μg FA once a week during the pre-pregnancy period.
arm group label: Multiple Micronutrient - 2
arm group type: Experimental
description: The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Multiple micronutrient groups 1 and 2 receive:
Vitamin A (μg) 800 Vitamin D (IU) 600 Vitamin E (mg) 10 Vitamin C (mg) 70 Thiamine (mg) 1.4 Riboflavin (mg) 1.4 Niacin (mg) 18 Vitamin B6 (mg) 1.9 Vitamin B12 (μg) 2.6 Folic acid (μg)* 2800 Iron (mg)* 60 Zinc (mg) 15 Copper (mg) 2 Selenium (μg) 65 Iodine (μg) 150
arm group label: Iron and Folic Acid - 2
arm group type: Active Comparator
description: The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Iron and folic acid groups 1 and 2 receive: iron (60mg) and folic acid (2800μg), based on current WHO recommendations for WRA.
arm group label: Folic acid - 2
arm group type: Placebo Comparator
description: The study population has been divided into 6 arms receiving 3 different pre-pregnancy interventions. The study uses a double blind design therefore the supplements are differentiated by a letter and a color: P/Purple, Q/Black, S/Brown, M/Green, T/Orange, H/Red. Folic acid groups 1 and 2 receive: 2800 μg FA once a week during the pre-pregnancy period.
intervention type: Dietary Supplement
intervention name: Multiple Micronutrient
description: There is no current recommendation for weekly MM supplements for WRA. Therefore, we propose a supplement that contains: The same amounts of iron and folic acid as the weekly, pre-natal IFA supplement; An amount of vitamin D based on the Food and Nutrition Board's Recommended Daily Allowances (RDA); UNICEF/WHO/UNU recommended amounts of remaining nutrients (UNIMMAP recommendations). The supplement is taken weekly during pre-pregnancy.
Vitamin A (μg) 800 Vitamin D (IU) 600 Vitamin E (mg) 10 Vitamin C (mg) 70 Thiamine (mg) 1.4 Riboflavin (mg) 1.4 Niacin (mg) 18 Vitamin B6 (mg) 1.9 Vitamin B12 (μg) 2.6 Folic acid (μg)* 2800 Iron (mg)* 60 Zinc (mg) 15 Copper (mg) 2 Selenium (μg) 65 Iodine (μg) 150
arm group label: Multiple Micronutrient - 2
arm group label: Multiple micronutrient - 1
intervention type: Dietary Supplement
intervention name: Iron and Folic Acid
description: The doses of weekly and daily iron (60mg) and folic acid (2800μg) are based on current WHO recommendations for WRA.
arm group label: Iron and Folic Acid - 2
arm group label: Iron and folic acid - 1
intervention type: Dietary Supplement
intervention name: Folic Acid
description: It is unethical to have a placebo group as FA is universally recommended for WRA to prevent neural tube defects. Therefore, the control group will receive 2800 μg FA once a week during the pre-pregnancy period. This dosage is safe and meets the minimum recommended intake of 400 μg/d for Women of Reproductive Age (WRA). Recent studies have shown that a weekly dose of 2800 μg FA is as effective as a daily dose of 400 μg in improving folic acid and reducing homocysteine levels among WRA.
arm group label: Folic Acid - 1
arm group label: Folic acid - 2
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Usha Ramakrishnan, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
country: Vietnam
citation: Nguyen PH, Lowe AE, Martorell R, Nguyen H, Pham H, Nguyen S, Harding KB, Neufeld LM, Reinhart GA, Ramakrishnan U. Rationale, design, methodology and sample characteristics for the Vietnam pre-conceptual micronutrient supplementation trial (PRECONCEPT): a randomized controlled study. BMC Public Health. 2012 Oct 24;12:898. doi: 10.1186/1471-2458-12-898.
PMID: 23092451
citation: Nguyen PH, Gonzalez-Casanova I, Young MF, Truong TV, Hoang H, Nguyen H, Nguyen S, DiGirolamo AM, Martorell R, Ramakrishnan U. Preconception Micronutrient Supplementation with Iron and Folic Acid Compared with Folic Acid Alone Affects Linear Growth and Fine Motor Development at 2 Years of Age: A Randomized Controlled Trial in Vietnam. J Nutr. 2017 Aug;147(8):1593-1601. doi: 10.3945/jn.117.250597. Epub 2017 Jun 14.
PMID: 28615372
citation: Nguyen PH, DiGirolamo AM, Gonzalez-Casanova I, Pham H, Hao W, Nguyen H, Truong TV, Nguyen S, Harding KB, Reinhart GA, Martorell R, Ramakrishnan U. Impact of preconceptional micronutrient supplementation on maternal mental health during pregnancy and postpartum: results from a randomized controlled trial in Vietnam. BMC Womens Health. 2017 Jun 17;17(1):44. doi: 10.1186/s12905-017-0401-3.
PMID: 28623904
citation: Nguyen PH, Young M, Gonzalez-Casanova I, Pham HQ, Nguyen H, Truong TV, Nguyen SV, Harding KB, Reinhart GA, Martorell R, Ramakrishnan U. Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam. PLoS One. 2016 Dec 5;11(12):e0167416. doi: 10.1371/journal.pone.0167416. eCollection 2016.
PMID: 27918586
citation: Ramakrishnan U, Nguyen PH, Gonzalez-Casanova I, Pham H, Hao W, Nguyen H, Truong TV, Nguyen S, Harding KB, Reinhart GA, Neufeld LM, Martorell R. Neither Preconceptional Weekly Multiple Micronutrient nor Iron-Folic Acid Supplements Affect Birth Size and Gestational Age Compared with a Folic Acid Supplement Alone in Rural Vietnamese Women: A Randomized Controlled Trial. J Nutr. 2016 Jul;146(7):1445S-52S. doi: 10.3945/jn.115.223420. Epub 2016 Jun 8.
PMID: 27281806
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Usha Ramakrishnan
investigator title: Professor
mesh term: Premature Birth
mesh term: Fetal Growth Retardation
mesh term: Iron Deficiencies
mesh term: Folic Acid
mesh term: Vitamin B Complex
mesh term: Micronutrients
mesh term: Trace Elements
sharing ipd: No