AnemiaNCT01665378
Impact of Pre-pregnancy Micronutrient Supplementation on Maternal and Child Outcomes
A study testing Multiple Micronutrient, Iron and Folic Acid and Folic Acid in people with Anemia and Intrauterine Growth Retardation, run by Emory University at 1 site in Vietnam.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Anemia, Intrauterine Growth Retardation, Preterm Delivery
- What is being tested?
- Multiple Micronutrient, Iron and Folic Acid and Folic Acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5,011 participants
- Where
- 1 siteVietnam
- Study dates
- Oct 2011to Aug 2023
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Child of a female participant of the original study
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Vietnam1 site
Thai Nguyen University of Medicine and Pharmacy
Thai Nguyen, Thái Nguyên, 24000
About this study
Official title: Impact of Pre-Pregnancy Micronutrient Supplementation on Maternal and Child Outcomes
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.
Read the 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.
Low birth weight (LBW) and anemia remain public health problems in many developing countries. There is a great deal of evidence in the literature that anemia, primarily due to iron deficiency, has been associated with poor birth outcomes and LBW. The most common interventions is the provision of iron-folate (IFA) supplements during pregnancy. Despite several decades of effort, the success of these interventions in improving anemia and LBW was limited due to: inadequate coverage, high costs and an inability to sustain the programs. Reasons for low effectiveness also include inadequacy of delivery systems, side effects and poor compliance among pregnant women. In addition, intervening with iron-folate (IFA) supplements during pregnancy alone may not be sufficient as many women enter pregnancy with suboptimal iron stores. Weekly pre-pregnancy IFA supplementation (WIFS) has been introduced as a way to reduce the burden of anemia and improve birth outcomes. WIFS has been shown to improve iron status and reduce the burden of anemia in Women of Reproductive Age (WRA) in the short term, but no study has assessed the effects of this intervention on birth outcomes.
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. The study will be conducted in Vietnam, a developing country, where anemia and Iron Deficiency (ID) are highly prevalent and will provide valuable scientific evidence that will inform policy. Infants born to women receiving the intervention are followed up to age 10 to 11 to assess periconception nutrition on early adolescent body size, anemic status, cognitive and academic achievement.
- Being tested
- Multiple Micronutrient, Iron and Folic Acid, Folic Acid
- Keywords
- prepregnancy, micronutrient, supplementation, maternal, child, health
- Medical subject headings
- Anemia, Fetal Growth Retardation, Premature Birth, Iron Deficiencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multiple MicronutrientDietary supplement
There is no current recommendation for weekly MM supplements for WRA. Therefore, the researchers 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/United Nations University (UNU) recommended amounts of remaining nutrients (UNIMMAP recommendations). The supplement is taken weekly during pre-pregnancy and contains:
- 800 μg Vitamin A
- 600 IU Vitamin D
- 10 mg Vitamin E
- 70 mg Vitamin C
- 1.4 mg Thiamine
- 1.4 mg Riboflavin
- 18 mg Niacin
- 1.9 mg Vitamin B6
- 2.6 μg Vitamin B12
- 2800 μg Folic Acid
- 60 mg Iron
- 15 mg Zinc
- 2 mg Copper
- 65 μg Selenium
- 150 μg Iodine
Iron and Folic AcidDietary supplement
The doses of weekly and daily iron (60mg) and folic acid (2800μg) are based on current WHO recommendations for WRA.
Folic AcidDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Multiple Micronutrient - 1 | 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 a supplement that is taken weekly during pre-pregnancy. Receives: Dietary Supplement: Multiple Micronutrient |
| Iron and Folic Acid - 1 | 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 World Health Organization (WHO) recommendations for WRA. Receives: Dietary Supplement: Iron and Folic Acid |
| Folic Acid - 1 | 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. Receives: Dietary Supplement: Folic Acid |
| Multiple Micronutrient - 2 | 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 a supplement that is taken weekly during pre-pregnancy. Receives: Dietary Supplement: Multiple Micronutrient |
| Iron and Folic Acid - 2 | 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. Receives: Dietary Supplement: Iron and Folic Acid |
| Folic Acid - 2 | 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. Receives: Dietary Supplement: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Birth Size - Weight
Infant weight is measured as early as possible within 24 hours after birth using standard procedures. All measurements are obtained in duplicate by the same data collector. Weight is measured in grams (g).
Measured: At birth
Birth Size - Body Length
Infant length is measured as early as possible within 24 hours after birth using standard procedures. All measurements are obtained in duplicate by the same data collector. Length is measured in millimeters (mm).
Measured: At birth
Birth Size - Head Circumference
Infant head circumference is measured as early as possible within 24 hours after birth using standard procedures. All measurements are obtained in duplicate by the same data collector. Head circumference is measured in millimeters (mm).
Measured: At birth
Gestational Age
Gestational age is calculated based on the date of last menstrual period. This method has been shown to be reliable in previous work and the researchers expect precise estimates since women will be visited weekly from baseline during the pre-pregnancy period. Women who have delivered babies in the past 6 months are excluded.
Measured: At birth
Child length
Child length, measured in millimeters (mm) is measured at birth, 1, 3, 6, 9, 12, 15, 18, and 24 months of age.
Measured: From Birth to 24 months
Child weight
Child weight, measured in grams (g), is measured at birth, 1, 3, 6, 9, 12, 15, 18, and 24 months of age.
Measured: From birth through 24 months of age
Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) Score
Child development is measured using the Bayley Scales of Infant and Toddler Development - Third Edition at 12 and 24 months of age. The Bayley-III is a standardized comprehensive assessment tool for assessing child development in children one month to 42 months old. The highest possible scaled score on each subtest is 19, and the lowest possible score is 1. Scores from 8 to 12 are considered average. Index scores for motor and language domains are derived from sums of the subtest scaled scores. Index scores range from 40-160 with higher scores indicating. Composite scores are calculated for the cognitive, language, and motor scales to compare children to a normative age-matched sample. Composite scores have a mean of 100 with a standard deviation of 15. Composite scores below 85 indicate mild cognitive impairment and scores below 70 indicate moderate to severe cognitive impairment.
Measured: 12 and 24 months
Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Score
Child development is measured using the WISC-IV. This test has been validated and adapted in the Vietnamese context and takes 60-70 minutes to administer. The WISC-IV consists of 10 subtests (Vocabulary, Similarities, Comprehension, Block Design, Picture Concepts, Matrix Reasoning, Digit Span, Letter-Number Sequencing, Coding, and Symbol search). These are summed into four indices: the Verbal Comprehension Index (VCI, a measure of crystallized abilities), Perceptual Reasoning Index (PRI, a measure of inductive and quantitative reasoning), Working Memory Index (WMI, a measure of children's ability to memorize new information), Processing Speed Index (PSI, a measure of the speed of information processing including the ability to focus attention and quickly scan, discriminate and sequentially order visual information). The Full-Scale intelligence quotient (IQ) score ranges from 40 to 160 points with higher scores indicating higher intelligence. Scores of 90 to 109 are considered average.
Measured: 6 to 7 years of age, 10 to 11 years of age
Weight-for-age Z score (WAZ)
The weight-for-age Z score (WAZ) is assessed 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.
Measured: 6 to 7 years of age, 10 to 11 years of age
Height-for-Age Z Score (HAZ)
The height-for-age Z score (HAZ) is assessed 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.
Measured: 6 to 7 years of age, 10 to 11 years of age
Weight-for-Height Z Score (WHZ)
The weight-for-height Z score (WHZ) is assessed 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.
Measured: 6 to 7 years of age
Body Mass Index Z Score (BMI-Z)
The body mass index Z Score (BMI-Z) is assessed 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.
Measured: 10 to 11 years of age
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
Measured: 6 to 7 years of age, 10 to 11 years of age
Secondary outcomes (4)
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).
Measured: At baseline, 1 month postpartum, 3 months postpartum
Infants' iron status
Infant iron status is measured in cord blood samples (5 ml) obtained at delivery and at 3 months of age using a capillary blood sample that is obtained from a heel prick. The hemoglobin concentration are measured from a drop of blood using the HEMOCUE B- Hb photometer. The blood samples are then centrifuged and serum samples are aliquoted 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.
Measured: Birth, 3 months of age
Center for Epidemiological Studies Depression Scale (CES-D) Score
Maternal depression is assessed with the Center for Epidemiological Studies Depression Scale (CES-D). The CES-D is a 20-item self-report instrument asking respondents if they have experienced symptoms of depression during the past week. Responses are given on a scale of 0 to 3 where rarely is scored as 0 and most of the time is scored as 3. Total scores range from 0 to 60 and higher scores indicate greater symptoms of depression.
Measured: At baseline, during pregnancy, 3 months postpartum
Edinburgh Postnatal Depression Scale (EPDS) Score
Maternal depression is assessed with the Edinburgh Postnatal Depression Scale (EPDS). The EPDS includes 10-items asking participants about symptoms of depression that they have experienced in the past 7 days. Responses are given on a 4-point scale where 0 corresponds with the least amount of symptoms and 3 corresponds with the highest amount of symptoms. Total scores range from 0 to 30 with higher scores indicating increased symptoms of depression. Scores of 10 and greater indicate possible depression.
Measured: At baseline, during pregnancy, 3 months postpartum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2012 (estimated)
- Study startOct 2011
- Primary completionSep 2014
- Study completionAug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5,011 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Micronutrient Initiative, The Mathile Institute for the Advancement of Human Nutrition, Thai Nguyen University of Medicine and Pharmacy
- Responsible party
- Principal investigator, Usha Ramakrishnan, Emory University
- Investigators
- Usha Ramakrishnan, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01665378
- Sponsor's protocol ID
- IRB00051384
- Other IDs
- 10-1196-UEMORY-01, 2025P009844
- Status last verified
- Sep 2026
- First submitted
- 13 Aug 2012
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23092451Nguyen 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.
PubMed 28623904Nguyen 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.
PubMed 27918586Ramakrishnan 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.
PubMed 27281806Nguyen 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.
PubMed 28615372Nguyen PT, Nguyen PH, Tran LM, Khuong LQ, Van Nguyen S, Young MF, DiGirolamo A, Ramakrishnan U. The Relationship of Preterm and Small for Gestational Age with Child Cognition During School-Age Years. J Nutr. 2024 Aug;154(8):2590-2598. doi: 10.1016/j.tjnut.2024.06.012. Epub 2024 Jun 25.
PubMed 38936548Ramakrishnan U, Wimalasena ST, Young MF, Khuong LQ, Tran LM, Hoffman DJ, Martorell R, Nguyen PH. Preconception Micronutrient Supplementation Affects Maternal BMI and Body Composition Postpartum: A Randomized Controlled Trial in Vietnam. J Nutr. 2024 Apr;154(4):1440-1448. doi: 10.1016/j.tjnut.2024.02.024. Epub 2024 Feb 26.
PubMed 38417549Duong C, Young MF, Nguyen PH, Tran L, Patel S, Ramakrishnan U. Temporal Dietary Diversity Patterns Are Associated with Linear Growth but Not Ponderal Growth in Young Children in Rural Vietnam. J Nutr. 2023 Oct;153(10):3083-3091. doi: 10.1016/j.tjnut.2023.06.030. Epub 2023 Jun 25.
PubMed 37364684Young 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.
PubMed 26454228Nguyen PH, Tran LM, Khuong LQ, Nguyen PT, Van Nguyen B, Be TH, Young MF, DiGirolamo AM, Martorell R, Ramakrishnan U. Preconception micronutrient supplementation positively affects offspring perceptual reasoning at 10-11 years of age: follow-up of a randomized controlled trial in Vietnam. Am J Clin Nutr. 2026 May;123(5):101270. doi: 10.1016/j.ajcnut.2026.101270. Epub 2026 Mar 12.
PubMed 41831611Young MF, Nguyen PH, Tran LM, Khuong LQ, Hendrix S, Martorell R, Ramakrishnan U. Maternal preconception BMI and gestational weight gain are associated with weight retention and maternal and child body fat at 6-7 years postpartum in the PRECONCEPT cohort. Front Nutr. 2023 May 26;10:1114815. doi: 10.3389/fnut.2023.1114815. eCollection 2023.
PubMed 37305082Gonzalez-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.
PubMed 28511688Young 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.
PubMed 28114316Nguyen 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.
PubMed 33693757Young MF, Nguyen P, Tran LM, Khuong LQ, Martorell R, Ramakrishnan U. Long-Term Association Between Maternal Preconception Hemoglobin Concentration, Anemia, and Child Health and Development in Vietnam. J Nutr. 2023 May;153(5):1597-1606. doi: 10.1016/j.tjnut.2023.03.015. Epub 2023 Mar 15.
PubMed 36925072