Back to resultsImpact of Pre-pregnancy Micronutrient Supplementation on Maternal and Child Outcomes
Primary Purpose
Anemia, Intrauterine Growth Retardation, Preterm Delivery
Status
Completed
Phase
Not Applicable
Locations
Vietnam
Study Type
Interventional
Intervention
Multiple Micronutrient
Iron and Folic Acid
Folic Acid
Sponsored by
About this trial
This is an interventional prevention trial for Anemia focused on measuring prepregnancy, micronutrient, supplementation, maternal, child, health
Eligibility Criteria
Inclusion Criteria:
- 18-35 years old
- Currently married
- Currently living in one of the 10 communes and intends to live in the areas for 24 months following recruitment
- 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
Sites / Locations
- Thainguyen University of Medicine and Pharmacy
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Active Comparator
Placebo Comparator
Experimental
Active Comparator
Placebo Comparator
Arm Label
Multiple micronutrient - 1
Iron and folic acid - 1
Folic Acid - 1
Multiple Micronutrient - 2
Iron and Folic Acid - 2
Folic acid - 2
Arm 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
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.
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.
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
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.
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.
Outcomes
Primary Outcome Measures
Birth Size
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
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.
Child growth
Length and weight will be measured at birth, 1, 3, 6, 9, 12, 15, 18, and 24 mo
Child development
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
Weight-for-age Z score (WAZ)
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
Height-for-age Z score (HAZ)
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
Weight -for-Height Z (WHZ) or Body Mass Index Z score (BMIZ)
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
Body composition (Lean mass/fat free mass index)
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
Secondary Outcome Measures
Mothers' iron status
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
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.
Maternal depression
Center for Epidemiological Studies Depression Scale (CES-D) and Edinburgh Postnatal Depression Scale (EPDS)
Full Information
NCT ID
NCT01665378
First Posted
August 13, 2012
Last Updated
July 7, 2021
Sponsor
Emory University
Collaborators
Micronutrient Initiative, The Mathile Institute for the Advancement of Human Nutrition
1. Study Identification
Unique Protocol Identification Number
NCT01665378
Brief Title
Impact of Pre-pregnancy Micronutrient Supplementation on Maternal and Child Outcomes
Official Title
Impact of Pre-Pregnancy Micronutrient Supplementation on Maternal and Child Outcomes
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
October 2011 (Actual)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
December 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
Micronutrient Initiative, The Mathile Institute for the Advancement of Human Nutrition
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Intrauterine Growth Retardation, Preterm Delivery, Iron Deficiency
Keywords
prepregnancy, micronutrient, supplementation, maternal, child, health
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
5011 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Multiple micronutrient - 1
Arm Type
Experimental
Arm 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 Title
Iron and folic acid - 1
Arm Type
Active Comparator
Arm 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 Title
Folic Acid - 1
Arm Type
Placebo Comparator
Arm 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 Title
Multiple Micronutrient - 2
Arm Type
Experimental
Arm 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 Title
Iron and Folic Acid - 2
Arm Type
Active Comparator
Arm 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 Title
Folic acid - 2
Arm Type
Placebo Comparator
Arm 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(s)
Multiple Micronutrient
Intervention 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
Intervention Type
Dietary Supplement
Intervention Name(s)
Iron and Folic Acid
Intervention Description
The doses of weekly and daily iron (60mg) and folic acid (2800μg) are based on current WHO recommendations for WRA.
Intervention Type
Dietary Supplement
Intervention Name(s)
Folic Acid
Intervention 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.
Primary Outcome Measure Information:
Title
Birth Size
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.
Time Frame
At birth
Title
Gestational Age
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.
Time Frame
At birth
Title
Child growth
Description
Length and weight will be measured at birth, 1, 3, 6, 9, 12, 15, 18, and 24 mo
Time Frame
From birth through 24 months
Title
Child development
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
Time Frame
Up to 7 years post enrollment
Title
Weight-for-age Z score (WAZ)
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
Time Frame
Up to 7 years post enrollment
Title
Height-for-age Z score (HAZ)
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
Time Frame
Up to 7 years post enrollment
Title
Weight -for-Height Z (WHZ) or Body Mass Index Z score (BMIZ)
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
Time Frame
Up to 7 years post enrollment
Title
Body composition (Lean mass/fat free mass index)
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
Time Frame
Up to 7 years post enrollment
Secondary Outcome Measure Information:
Title
Mothers' iron status
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).
Time Frame
At baseline and 1 and 3 months post partum
Title
Infants' iron status
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.
Time Frame
1 and 3 months of age
Title
Maternal depression
Description
Center for Epidemiological Studies Depression Scale (CES-D) and Edinburgh Postnatal Depression Scale (EPDS)
Time Frame
At baseline, during pregnancy, 3 months postpartum
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
18-35 years old
Currently married
Currently living in one of the 10 communes and intends to live in the areas for 24 months following recruitment
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Usha Ramakrishnan, PhD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thainguyen University of Medicine and Pharmacy
City
Hành Phố Thái Nguyên
State/Province
Thái Nguyên
ZIP/Postal Code
24000
Country
Vietnam
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23092451
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.
Results Reference
background
PubMed Identifier
28615372
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.
Results Reference
background
PubMed Identifier
28623904
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.
Results Reference
result
PubMed Identifier
27918586
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.
Results Reference
result
PubMed Identifier
27281806
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.
Results Reference
result
PubMed Identifier
33693757
Citation
Nguyen PH, Young MF, Khuong LQ, Tran LM, Duong TH, Nguyen HC, Martorell R, Ramakrishnan U. Maternal Preconception Body Size and Early Childhood Growth during Prenatal and Postnatal Periods Are Positively Associated with Child-Attained Body Size at Age 6-7 Years: Results from a Follow-up of the PRECONCEPT Trial. J Nutr. 2021 May 11;151(5):1302-1310. doi: 10.1093/jn/nxab004.
Results Reference
derived
PubMed Identifier
28511688
Citation
Gonzalez-Casanova I, Nguyen PH, Young MF, Harding KB, Reinhart G, Nguyen H, Nechitillo M, Truong TV, Pham H, Nguyen S, Neufeld LM, Martorell R, Ramakrishnan U. Predictors of adherence to micronutrient supplementation before and during pregnancy in Vietnam. BMC Public Health. 2017 May 16;17(1):452. doi: 10.1186/s12889-017-4379-4.
Results Reference
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PubMed Identifier
28114316
Citation
Young MF, Hong Nguyen P, Addo OY, Pham H, Nguyen S, Martorell R, Ramakrishnan U. Timing of Gestational Weight Gain on Fetal Growth and Infant Size at Birth in Vietnam. PLoS One. 2017 Jan 23;12(1):e0170192. doi: 10.1371/journal.pone.0170192. eCollection 2017.
Results Reference
derived
PubMed Identifier
28077098
Citation
Deputy NP, Nguyen PH, Pham H, Nguyen S, Neufeld L, Martorell R, Ramakrishnan U. Validity of gestational age estimates by last menstrual period and neonatal examination compared to ultrasound in Vietnam. BMC Pregnancy Childbirth. 2017 Jan 11;17(1):25. doi: 10.1186/s12884-016-1192-5.
Results Reference
derived
PubMed Identifier
26454228
Citation
Young MF, Nguyen PH, Addo OY, Hao W, Nguyen H, Pham H, Martorell R, Ramakrishnan U. The relative influence of maternal nutritional status before and during pregnancy on birth outcomes in Vietnam. Eur J Obstet Gynecol Reprod Biol. 2015 Nov;194:223-7. doi: 10.1016/j.ejogrb.2015.09.018. Epub 2015 Sep 28.
Results Reference
derived
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Impact of Pre-pregnancy Micronutrient Supplementation on Maternal and Child Outcomes
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