Trial record 5 of 37 for:    (antenatal OR prenatal) AND folic acid

Impact of Pre-pregnancy Micronutrient Supplementation on Maternal and Child Outcomes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
MicroNutrient Initiative
Mathile Institute for Advancement in Human Nutrition
Information provided by (Responsible Party):
Dr. Usha Ramakrishnan, Emory University
ClinicalTrials.gov Identifier:
NCT01665378
First received: August 13, 2012
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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. We propose a double blind randomized controlled trial in rural Vietnam to evaluate the efficacy of weekly pre- pregnancy IFA or Multiple Micronutrient (MM) supplements on birth outcomes and maternal and infant iron status compared to providing only prenatal IFA supplements. This project is a collaborative effort between Emory University, USA and Thainguyen University of Medicine and Pharmacy, Vietnam. Eligible and willing women of reproductive age (WRA) will be assigned randomly to one of the following 3 groups of pre-pregnancy weekly supplementation: 1) FA (control) 2) IFA and 3) MM. All women will receive daily IFA when pregnant. We will recruit ~ 5000 WRA to obtain a sample of at least 1650 mother-infant pairs, which, at 90% power, will allow us to detect differences of ~ 60 g in birth weight between any two groups. Data on obstetric history, socio-demographic status, iron status, anthropometry and dietary intakes will be obtained at baseline. Key outcome measures will be 1) offspring's size and gestational age at birth 2) offspring's iron status at birth and 3 months of age and 3) maternal iron status at the beginning of pregnancy, 1 and 3 months post-partum. Intention to treat approach will be used to compare the various intervention groups. This study is timely and responds to the WHO Global Expert Consultation (2007) which identified the need to evaluate the long term benefits of weekly IFA and MM supplementation in WRA. The findings will provide the necessary evidence to policy makers to recommend weekly MM or IFA supplements to WRA to improve birth outcomes. The central hypothesis is that pre-pregnancy weekly IFA or MM supplementation followed by prenatal IFA and MM supplementation respectively, will improve birth outcomes as well as maternal and infant iron status compared to current practice of providing only prenatal IFA supplements. This hypothesis will be tested by conducting a randomized double-blinded placebo-controlled trial in Vietnam.


Condition Intervention Phase
Anemia
Intrauterine Growth Retardation
Preterm Delivery
Iron Deficiency
Dietary Supplement: Multiple Micronutrient
Dietary Supplement: Iron and Folic Acid
Dietary Supplement: Folic Acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of Pre-Pregnancy Micronutrient Supplementation on Maternal and Child Outcomes

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Birth Size [ Time Frame: At birth ] [ Designated as safety issue: No ]
    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.

  • Gestational Age [ Time Frame: At birth ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mothers' iron status [ Time Frame: At baseline and 1 and 3 months post partum ] [ Designated as safety issue: No ]
    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).

  • Infants' iron status [ Time Frame: 1 and 3 months of age ] [ Designated as safety issue: No ]

    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.



Enrollment: 5011
Study Start Date: October 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Multiple micronutrient - 1

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

Dietary Supplement: Multiple Micronutrient

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

Active Comparator: Iron and folic acid - 1
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.
Dietary Supplement: Iron and Folic Acid
The doses of weekly and daily iron (60mg) and folic acid (2800μg) are based on current WHO recommendations for WRA.
Placebo Comparator: Folic Acid - 1
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.
Dietary Supplement: Folic Acid
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.
Experimental: Multiple Micronutrient - 2

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

Dietary Supplement: Multiple Micronutrient

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

Active Comparator: Iron and Folic Acid - 2
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.
Dietary Supplement: Iron and Folic Acid
The doses of weekly and daily iron (60mg) and folic acid (2800μg) are based on current WHO recommendations for WRA.
Placebo Comparator: Folic acid - 2
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.
Dietary Supplement: Folic Acid
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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18-35 years old
  • Currently married
  • Intends to live in the study area for the next 24 months
  • Plans to have children in the next year
  • Agrees to participate with informed consent

Exclusion Criteria:

  • Currently pregnant
  • Delivered in the previous six months
  • Regularly consumed IFA or MM supplements in the past 2 months
  • Severe anemia (Hb < 7 g/L)
  • History of high risk pregnancy including abruptio placenta, placenta previa, gestational diabetes, pregnancy induced hypertension, coagulation disorders, thrombocytopenia or chronic vascular, renal or systemic disease and drug use
  • Chronic hematological diseases, hereditary defects of red cells or hemoglobin
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01665378

Locations
Vietnam
Thainguyen University of Medicine and Pharmacy
Thainguyen, Vietnam
Sponsors and Collaborators
Emory University
MicroNutrient Initiative
Mathile Institute for Advancement in Human Nutrition
Investigators
Principal Investigator: Usha Ramakrishnan, PhD Emory University
  More Information

Publications:
Responsible Party: Dr. Usha Ramakrishnan, Professor, Emory University
ClinicalTrials.gov Identifier: NCT01665378     History of Changes
Other Study ID Numbers: IRB00051384, 10-1196-UEMORY-01
Study First Received: August 13, 2012
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board
Vietnam: Thainguyen University of Medicine and Pharmacy

Keywords provided by Emory University:
prepregnancy
micronutrient
supplementation
maternal
child
health

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Anemia
Fetal Growth Retardation
Premature Birth
Anemia, Iron-Deficiency
Hematologic Diseases
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes
Obstetric Labor, Premature
Obstetric Labor Complications
Anemia, Hypochromic
Iron Metabolism Disorders
Metabolic Diseases
Hematinics
Iron
Micronutrients
Trace Elements
Vitamins
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014