Trial of Pre-Pregnancy Supplements (TOPPS)

The purpose of this study is to determine whether daily oral supplements of multivitamins (including vitamins B-complex, C and E) along with Iron and folic acid given to non-pregnant women results in lower prevalence of anemia in preparation for pregnancy when compared to daily iron and folic acid supplements or folic acid alone.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Dietary supplement: Folic Acid and Iron; Dietary supplement: Folic Acid; Dietary supplement: Multivitamins, Folic Acid, and Iron

Detailed Description

Globally, more than half a million women die from pregnancy or childbirth-related complications, most of them in developing countries. The global community committed to reducing the maternal mortality ratio by three quarters between 1990 and 2015 (MDG5). Women die from a range of complications in pregnancy, childbirth or the postpartum period. 80% of maternal deaths are due to severe bleeding (mostly bleeding postpartum), infections, hypertensive disorders in pregnancy and obstructed labor. Additionally, low birth weight and neonatal mortality are common problems in developing countries. The benefit of periconceptual folate on preventing congenital anomalies has been established in randomized trials; however, the role of other nutrients needs to be examined further. Anemia is strongly associated with adverse perinatal outcomes including maternal mortality and low birthweight.

• Study Type: Interventional
• Enrollment (Actual): 802
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Tanzania
  • Rufiji, Tanzania
    • Ifakara Health Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 29 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Girls aged > =15 years and <= 29 years
2. Have not missed a menstrual period during recruitment (no amenorrhea)
3. Has not been pregnant or given birth within the last 6 months
4. Intend to stay in the study area for at least 6 months after enrollment
5. Have provided written informed consent

Exclusion Criteria:

1. Amenorrhea or confirmed pregnancy at screening or enrollment.
2. Has given birth within 6 months
3. Already taking long-term vitamin supplementation.
4. Any severe illness requiring hospitalization at screening or enrollment (women who have been deemed to have recovered will be eligible once they return home).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Folic Acid and Iron; 0.4mg of folic acid and 30 mg elemental iron taken daily for 6 months	Dietary supplement: Folic Acid and Iron; Daily oral dose of 30 mg elemental iron, 0.4 mg folic acid
Placebo Comparator: Folic Acid; 0.4mg of folic acid taken daily for 6 months	Dietary supplement: Folic Acid; Daily oral dose of 0.4 mg folic acid
Active Comparator: Multivitamins, Folic Acid, and Iron; A multivitamin and micronutrient supplement that constitutes 1 RDA of Vitamins A (2500 IU), B1 (1.4 mg), B2 (1.4 mg), B6 (1.9 mg), B12 (2.6 ug), niacin (18 mg), C (70 mg), E (10 mg), and folic acid (0.4 mg)along with 30 mg of elemental iron taken daily for 6 months.	Dietary supplement: Multivitamins, Folic Acid, and Iron; Daily oral dose containing 2500 IU Vitamin A, 1.4 mg Vitamin B1, 1.4 mg Vitamin B2, 2.6 mg Vitamin B12, 1.9 mg Vitamin B6, 18 mg Niacin, 70 mg Vitamin C, 14.9 IU Vitamin E, 30 mg elemental iron, 0.4 mg folic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anemia	Anemia will be defined as hemoglobin < 12gm/dL at 6 months of intervention. Hemoglobin concentration will also be analyzed as a continuous outcome.	6 months following the start of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Gain during intervention	Weight gain during intervention will be defined as the difference in weight between weight at randomization and weight at 6 months of intervention.	6 months following the start of the intervention
Mid Upper Arm Circumference		6 months following the start of the intervention
Peripheral malaria parasitemia	Peripheral malaria parasitemia will be defined as fever in the past 72 hours with any malaria parasitemia in peripheral blood.	6 months following the start of the intervention

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: Ifakara Health Institute
• Investigators: Principal Investigator: Honorati M Masanja, PhD, Ifakara Health Institute

Publications and helpful links

General Publications

• Gunaratna NS, Masanja H, Mrema S, Levira F, Spiegelman D, Hertzmark E, Saronga N, Irema K, Shuma M, Elisaria E, Fawzi W. Multivitamin and iron supplementation to prevent periconceptional anemia in rural tanzanian women: a randomized, controlled trial. PLoS One. 2015 Apr 23;10(4):e0121552. doi: 10.1371/journal.pone.0121552. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: August 13, 2010
• First Submitted That Met QC Criteria: August 13, 2010
• First Posted (Estimate): August 17, 2010

Study Record Updates

• Last Update Posted (Estimate): September 11, 2012
• Last Update Submitted That Met QC Criteria: September 8, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: iron; folate; multivitamins; periconception
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Trace Elements; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex; Iron
• Other Study ID Numbers: 0055/07