Overview

This trial is active, not recruiting.

Conditions anemia, intrauterine growth retardation, preterm delivery, iron deficiency
Treatments multiple micronutrient, iron and folic acid, folic acid
Phase phase 3
Sponsor Emory University
Collaborator Micronutrient Initiative
Start date October 2011
End date September 2014
Trial size 5011 participants
Trial identifier NCT01665378, 10-1196-UEMORY-01, IRB00051384

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Experimental)
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
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)
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.
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)
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.
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)
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
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)
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.
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)
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.
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.

Primary Outcomes

Measure
Birth Size
time frame: At birth
Gestational Age
time frame: At birth
Child growth
time frame: From birth through 24 months
Child development
time frame: At 12 and 24 months

Secondary Outcomes

Measure
Mothers' iron status
time frame: At baseline and 1 and 3 months post partum
Infants' iron status
time frame: 1 and 3 months of age
Maternal depression
time frame: At baseline, during pregnancy, 3 months postpartum

Eligibility Criteria

Female participants from 18 years up to 35 years old.

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

Additional Information

Official title Impact of Pre-Pregnancy Micronutrient Supplementation on Maternal and Child Outcomes
Principal investigator Usha Ramakrishnan, PhD
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Emory University.