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

NCT01665378 | Completed

• 2 other identifiers: IRB0005138410-1196-UEMORY-01
• Study Type: interventional
• Target: 5,011
• Locations: 1 country
• Sites: 1

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.

Conditions

Anemia; Intrauterine Growth Retardation; Preterm Delivery; Iron Deficiency

Keywords

prepregnancy; micronutrient; supplementation; maternal; child; health

Outcome Measures

Primary Outcomes (8)

• 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.

  At birth

• 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.

  At birth

• Child growth

  Length and weight will be measured at birth, 1, 3, 6, 9, 12, 15, 18, and 24 mo

  From birth through 24 months

• 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

  Up to 7 years post enrollment

• 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

  Up to 7 years post enrollment

• 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

  Up to 7 years post enrollment

• 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

  Up to 7 years post enrollment

• 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

  Up to 7 years post enrollment

Secondary Outcomes (3)

• Mothers' iron status

  At baseline and 1 and 3 months post partum

• Infants' iron status

  1 and 3 months of age

• Maternal depression

  At baseline, during pregnancy, 3 months postpartum

Study Arms (6)

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: 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

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 WHO recommendations for WRA.

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.

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: 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

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.

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.

Dietary Supplement: Folic Acid

Interventions

Multiple Micronutrient DIETARY_SUPPLEMENT

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

Multiple Micronutrient - 2; Multiple micronutrient - 1

Iron and Folic Acid DIETARY_SUPPLEMENT

The doses of weekly and daily iron (60mg) and folic acid (2800μg) are based on current WHO recommendations for WRA.

Iron and Folic Acid - 2; Iron and folic acid - 1

Folic Acid DIETARY_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.

Folic Acid - 1; Folic acid - 2

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Micronutrient Initiative: collaborator
• The Mathile Institute for the Advancement of Human Nutrition: collaborator

Study Sites (1)

Thainguyen University of Medicine and Pharmacy

Hành Phố Thái Nguyên, Thái Nguyên, 24000, Vietnam

Location

Related Publications (15)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Nguyen 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.

  PMID: 38936548 DERIVED

• Ramakrishnan 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.

  PMID: 38417549 DERIVED

• Duong 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.

  PMID: 37364684 DERIVED

• Young 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.

  PMID: 36925072 DERIVED

• Tran LM, Nguyen PH, Young MF, Ramakrishnan U, Alderman H. Home environment and nutritional status mitigate the wealth gap in child development: a longitudinal study in Vietnam. BMC Public Health. 2023 Feb 8;23(1):286. doi: 10.1186/s12889-023-15156-2.

  PMID: 36755279 DERIVED

• 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.

  PMID: 33693757 DERIVED

• 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.

  PMID: 28511688 DERIVED

• 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.

  PMID: 28114316 DERIVED

• 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.

  PMID: 28077098 DERIVED

• 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.

  PMID: 26454228 DERIVED

MeSH Terms

Conditions

Anemia; Fetal Growth Retardation; Premature Birth; Iron Deficiencies

Interventions

Iron; Folic Acid

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Usha Ramakrishnan, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 13, 2012
• First Posted: August 15, 2012
• Study Start: October 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2019
• Last Updated: July 8, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)