Long-term Iron Supplements and Malaria Risk in Early Pregnancy: a Randomized Controlled Trial (PALUFER)

Malaria Risk Prior to and During Early Pregnancy in Nulliparous Women Receiving Long-term Weekly Iron and Folic Acid Supplementation (WIFS): a Non-inferiority Randomized Controlled Trial

A randomized double-blind controlled trial will be carried out in which young, nulliparous (having never given birth) women will be randomly assigned to receive weekly supplementation with either iron and folic acid or folic acid alone. Women will be followed-up weekly up to 18 months. Women who become pregnant will be followed-up until delivery. Malaria risk in both groups will be compared by assessing the prevalence of peripheral parasitaemia at the first antenatal clinic visit for pregnant women and at the end of the first malaria transmission season for non-pregnant women. The incidence of clinical malaria will be assessed by active and passive case detection throughout the follow-up period.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Dietary supplement: Folic Acid; Dietary supplement: Folic Acid and Iron

• Study Type: Interventional
• Enrollment (Actual): 1959
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Burkina Faso
  • Bobo-Dioulasso 01, Burkina Faso, 01 B.P. 545
    • Institute de Recherche en Sciences de la Sante, Direction Regionale de l'Ouest (IRSS-DRO) - / Centre Muraz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female
• At least 15 and less than 25 years old at enrolment
• Never given birth
• Resident within the Demographic Surveillance System (DSS) area
• Willing to adhere to the study requirements (including weekly observed drug intake)
• Provision of written informed consent (if non emancipated minor by guardian/parent with minor's assent

Exclusion Criteria:

• No menses for >3 months and/or palpable uterus or positive pregnancy test if history unclear
• Concurrent enrolment in another study
• Intention to move out of the study area for more than 2 months within the next 18 months
• Any significant illness at the time of screening that requires hospitalization, including clinical signs of severe anaemia (conjunctival or mucosal pallor, tachycardia, respiratory distress)
• History or presence of major clinical disease likely to influence pregnancy outcome (sickle cell disease, diabetes mellitus, severe renal or heart disease, open tuberculosis, epilepsy)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Folic Acid; 2.8mg of Folic Acid given weekly	Dietary supplement: Folic Acid; 2.8mg
Experimental: Folic Acid and Iron; 2.8mg Folic Acid and 60mg Iron given weekly	Dietary supplement: Folic Acid and Iron; 60mg Iron and 2.8mg Folic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of peripheral parasitaemia at first antenatal clinic visit (13-16 weeks gestation)	Completed	Nov 2013

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
a) In the pregnant cohort: Prevalence of iron deficiency at first antenatal visit	Completed	Sept 2013
a) In the pregnant cohort: Prevalence of anaemia at first antenatal clinic visit	Completed	Sept 2013
a) In the pregnant cohort: Incidence of clinical malaria during the first and subsequent trimesters	Completed	Jan 2014
a) In the pregnant cohort: Incidence of adverse pregnancy outcomes	Completed	Jan 2014
a) In the pregnant cohort: Mean birth weight and prevalence of low birth weight (<2500g)	Completed	Jan 2014
a) In the pregnant cohort: Mean gestational age at delivery	Completed	Jan 2014
a) In the pregnant cohort: Prevalence of placental malaria	Completed	Jan 2014
a) In the non-pregnant cohort: Prevalence of peripheral parasitaemia during the first rainy season after at least six months of supplementation	Completed	Nov 2012
a) In the non-pregnant cohort: Incidence of clinical malaria	Completed	Nov 2013
a) In the non-pregnant cohort: Incidence of gastrointestinal adverse events	Completed	Nov 2013
a) In the non-pregnant cohort: Prevalence of iron deficiency after at least 18 months supplementation	Completed	Nov 2013
a) In the non-pregnant cohort: Prevalence of anaemia after at least 18 months supplementation	Completed	Nov 2013
a) In the non-pregnant cohort: Adherence to supplementation	Completed	Nov 2013
a) In the non-pregnant cohort: Acceptability of weekly supplementation	Completed	June 2013
In the non-pregnant cohort: Prevalence of bacterial vaginosis at end assessment	Completed	Nov 2013
a) In the non-pregnant cohort: Prevalence of bacterial vaginosis at end assessment	Completed	Nov 2013
a) In the non-pregnant cohort: Prevalence of bacterial vaginosis at first antenatal visit	Completed	Nov 2013
a) In the non-pregnant cohort: Prevalence of iron deficiency at key study visits	Completed	Nov 2013
a) In the non-pregnant cohort: Prevalence of peripheral parasitaemia at end assessment	Completed	Nov 2013

Collaborators and Investigators

• Sponsor: Liverpool School of Tropical Medicine
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH); Institute of Tropical Medicine, Belgium; University of Manchester; Centre Muraz; Institut de Recherche en Sciences de la Sante-Direction Regionale de l'Ouest
• Investigators: Study Director: Bernard J BRABIN, Professor, Liverpool School of Tropical Medicine; Principal Investigator: Sabine GIES, MD, MTropMed, PhD, Clinical Research Unit Nanoro (CRUN)

Publications and helpful links

General Publications

• Brabin B, Tinto H, Roberts SA. Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area. Malar J. 2019 Nov 26;18(1):374. doi: 10.1186/s12936-019-3013-6.
• Brabin B, Gies S, Roberts SA, Diallo S, Lompo OM, Kazienga A, Brabin L, Ouedraogo S, Tinto H. Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso. Malar J. 2019 May 6;18(1):161. doi: 10.1186/s12936-019-2797-8.
• Diallo S, Roberts SA, Gies S, Rouamba T, Swinkels DW, Geurts-Moespot AJ, Ouedraogo S, Ouedraogo GA, Tinto H, Brabin BJ. Malaria early in the first pregnancy: Potential impact of iron status. Clin Nutr. 2020 Jan;39(1):204-214. doi: 10.1016/j.clnu.2019.01.016. Epub 2019 Jan 26.
• Gies S, Diallo S, Roberts SA, Kazienga A, Powney M, Brabin L, Ouedraogo S, Swinkels DW, Geurts-Moespot AJ, Claeys Y, D'Alessandro U, Tinto H, Faragher B, Brabin B. Effects of Weekly Iron and Folic Acid Supplements on Malaria Risk in Nulliparous Women in Burkina Faso: A Periconceptional, Double-Blind, Randomized Controlled Noninferiority Trial. J Infect Dis. 2018 Aug 24;218(7):1099-1109. doi: 10.1093/infdis/jiy257.
• Compaore A, Gies S, Brabin B, Tinto H, Brabin L. Community approval required for periconceptional adolescent adherence to weekly iron and/or folic acid supplementation: a qualitative study in rural Burkina Faso. Reprod Health. 2018 Mar 14;15(1):48. doi: 10.1186/s12978-018-0490-y.
• Brabin L, Roberts SA, Gies S, Nelson A, Diallo S, Stewart CJ, Kazienga A, Birtles J, Ouedraogo S, Claeys Y, Tinto H, d'Alessandro U, Faragher EB, Brabin B. Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso. BMC Med. 2017 Nov 23;15(1):206. doi: 10.1186/s12916-017-0967-5.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: September 27, 2010
• First Submitted That Met QC Criteria: September 27, 2010
• First Posted (Estimate): September 28, 2010

Study Record Updates

• Last Update Posted (Estimate): March 19, 2014
• Last Update Submitted That Met QC Criteria: March 18, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Pregnancy; Iron supplementation; Iron deficiency; Burkina Faso
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Physiological Effects of Drugs; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex
• Other Study ID Numbers: 10.55; 1U01HD061234-01A1 (U.S. NIH Grant/Contract)